^
Contact us  to learn more about
our Premium Content:  News alerts, weekly reports and conference planners
BIOMARKER:

MRE11A mutation

i
Other names: MRE11A, ATLD, MRE11, MRE11 meiotic recombination 11 homolog A (S. cerevisiae)
Entrez ID:
Related biomarkers:
2ms
Trial completion • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • BAP1 (BRCA1 Associated Protein 1) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • WRN (WRN RecQ Like Helicase) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)
|
HER-2 positive • BRCA2 mutation • BRCA1 mutation • HR positive • HER-2 negative • ATM mutation • PALB2 mutation • CDK12 mutation • BAP1 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • HR positive + HER-2 negative • RAD50 mutation • BARD1 mutation • BLM mutation • CHEK1 mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation • PTEN mutation + HR positive • CHEK1 expression • HER-2 negative + HR positive + BRCA mutation
|
Herceptin (trastuzumab) • Zejula (niraparib) • Puyouheng (pucotenlimab)
7ms
A rare case of TFEB/6p21/VEGFA-amplified renal cell carcinoma diagnosed by whole-exome sequencing: clinicopathological and genetic feature report and literature review. (PubMed, Diagn Pathol)
We clarified the patient's challenging diagnosis and discussed the clinicopathology, immunophenotype, differential diagnosis, and molecular genetic information regarding TFEB/6p21/VEGFA-amplified RCC via exome analysis and a literature review.
Review • Journal • Tumor mutational burden • PARP Biomarker • PD(L)-1 Biomarker • IO biomarker
|
TMB (Tumor Mutational Burden) • ATM (ATM serine/threonine kinase) • VEGFA (Vascular endothelial growth factor A) • CDH1 (Cadherin 1) • TFE3 (Transcription Factor Binding To IGHM Enhancer 3) • MRE11A (MRE11 homolog, double strand break repair nuclease) • CCND3 (Cyclin D3) • MME (Membrane Metalloendopeptidase) • TGFB1 (Transforming Growth Factor Beta 1) • MLANA (Melan-A) • TFEB (Transcription Factor EB 2)
|
ATM mutation • TMB-L • MRE11A mutation • TFE3 translocation
|
Lynparza (olaparib) • Talzenna (talazoparib) • Zejula (niraparib) • Rubraca (rucaparib)
7ms
Enrollment open
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDK12 (Cyclin dependent kinase 12) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)
|
BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • BARD1 mutation • BLM mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation • RAD51 mutation
9ms
Evaluation of a Multimodal Strategy for Early Diagnosis of Men at High Genetic Risk of Prostate Cancer (HRPCa-II) (clinicaltrials.gov)
P=N/A, N=880, Not yet recruiting, Assistance Publique - Hôpitaux de Paris | Trial completion date: Nov 2027 --> Jul 2029 | Trial primary completion date: Nov 2027 --> Jul 2029
Trial completion date • Trial primary completion date
|
TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • HOXB13 (Homeobox B13)
|
BRCA1 mutation • PTEN mutation • PALB2 mutation • BRIP1 mutation • MSH2 mutation • RAD51C mutation • RAD51D mutation • RAD50 mutation • BARD1 mutation • BLM mutation • MRE11A mutation • MLH3 mutation • NBN mutation
11ms
SUKSES-B2: Olaparib and Bevacizumab in Relapsed Small Cell Lung Cancer Subjects (clinicaltrials.gov)
P2, N=25, Completed, Se-Hoon Lee | Recruiting --> Completed | Trial primary completion date: Jun 2023 --> Oct 2023
Trial completion • Trial primary completion date • Combination therapy
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • SLFN11 (Schlafen Family Member 11) • BRCA (Breast cancer early onset) • RAD51 (RAD51 Homolog A) • RAD51B (RAD51 Paralog B) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • WRN (WRN RecQ Like Helicase) • POU2F3 (POU Class 2 Homeobox 3) • RAD52 (RAD52 Homolog DNA Repair Protein) • RECQL5 (RecQ Like Helicase 5) • RECQL (RecQ Like Helicase) • RECQL4( RecQ Like Helicase 4) • RPA1 (Replication Protein A1)
|
BRCA2 mutation • BRCA1 mutation • RAD51C mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • BLM mutation • BRCA mutation • MRE11A mutation • RAD54L mutation • NBN mutation • RAD52 mutation • RECQL mutation • RECQL4 mutation • RECQL5 mutation
|
Avastin (bevacizumab) • Lynparza (olaparib)
12ms
Trial initiation date
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDK12 (Cyclin dependent kinase 12) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)
|
BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • BARD1 mutation • BLM mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation • RAD51 mutation
12ms
A multicohort phase 2 trial of ADT, docetaxel plus nivolumab in patients with de novo metastatic hormone-sensitive prostate cancer enriched for inflamed tumors and DNA damage repair defects. (ASCO-GU 2024)
After January 2022, the addition of standard of care abiraterone/prednisone was allowed after 7 months of study treatment at investigator discretion. Clinical trial information: NCT04126070.PD-L1 Combined Positive Score (CPS) ≥ 1 and/or CD T cell density ≥ 200. Homozygous deletions and/or deleterious mutations in a DDR gene, including and not limited to BRCA2, ATM, CHECK2, BRCA1, PALB2, RAD51D, ATR, NBN, PMS2, GEN1, MLH1, MSH2, MSH6, RAD51C, MRE11A, BRIP1, FAM175A, and CDK12.
P2 data • Clinical • PD(L)-1 Biomarker • BRCA Biomarker • IO biomarker • Metastases
|
PD-L1 (Programmed death ligand 1) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CD8 (cluster of differentiation 8) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CDK12 (Cyclin dependent kinase 12) • PMS2 (PMS1 protein homolog 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • ABRAXAS1 (Abraxas 1 BRCA1 A Complex Subunit 2) • GEN1 (GEN1 Holliday junction 5' flap endonuclease)
|
PD-L1 expression • ATM mutation • PALB2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • PMS2 mutation • MRE11A mutation • NBN mutation
|
OncoPanel™ Assay
|
Opdivo (nivolumab) • docetaxel • abiraterone acetate
1year
Comprehensive genomic profiling (CGP) unravels somatic BRCA (sBRCA) and homologous recombinant repair (HRR) gene alterations across multi-cancer spectrum (ESMO Asia 2023)
60% patients with sBRCA and HRR mutations treated with platinum / PARPi as NACT, achieved partial to pathological complete response (pCR) while 5 cases treated with IO are on follow up. Conclusions CGP identified sBRCA and HRR mutations in wide spectrum of cancers enabling the utility of PARPi as maintenance therapy, hence necessitating sBRCA and HRR testing as standard of care besides germline testing for personalized therapy.
Tumor mutational burden • PARP Biomarker • BRCA Biomarker • IO biomarker
|
TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • ARID1A (AT-rich interaction domain 1A) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • ATRX (ATRX Chromatin Remodeler) • BRCA (Breast cancer early onset) • RAD51 (RAD51 Homolog A) • RAD50 (RAD50 Double Strand Break Repair Protein) • MRE11A (MRE11 homolog, double strand break repair nuclease)
|
BRCA1 mutation • RAD50 mutation • MRE11A mutation
|
TruSight Oncology 500 Assay
1year
Trial suspension
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDK12 (Cyclin dependent kinase 12) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)
|
BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • BARD1 mutation • BLM mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation • RAD51 mutation
over1year
Trial initiation date
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDK12 (Cyclin dependent kinase 12) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)
|
BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • BARD1 mutation • BLM mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation • RAD51 mutation
over1year
Trial initiation date
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDK12 (Cyclin dependent kinase 12) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)
|
BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • BARD1 mutation • BLM mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation • RAD51 mutation
over1year
Enrollment open
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDK12 (Cyclin dependent kinase 12) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)
|
BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • BARD1 mutation • BLM mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation • RAD51 mutation
over1year
The application of a multigene NGS assay in homologous recombination deficiency tracking. (ASCO 2023)
A high rate of HR mutations was detected in ovarian, breast and prostate which is consistent with the PARPi approval in these tumor types. The presence of BRCA1/2 mutations was highly associated with increased LOH value whereas it did not correlate to other HR mutations. Additionally, the pancancer presence of HR gene alterations indicates that the use of such genes as biomarkers of platinum and PARPi treatments should be evaluated in a wider range of tumor types.
Tumor mutational burden • PARP Biomarker • BRCA Biomarker • IO biomarker • Next-generation sequencing
|
KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • HRD (Homologous Recombination Deficiency) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1) • PALB2 (Partner and localizer of BRCA2) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD50 (RAD50 Double Strand Break Repair Protein) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • WRN (WRN RecQ Like Helicase)
|
TP53 mutation • KRAS mutation • BRCA2 mutation • BRCA1 mutation • HRD • ATM mutation • ARID1A mutation • PALB2 mutation • BAP1 mutation • BRIP1 mutation • RAD50 mutation • BARD1 mutation • BLM mutation • MRE11A mutation • NBN mutation • CHEK1 expression
|
OncoScan™ CNV Assay
almost2years
New P1 trial
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDK12 (Cyclin dependent kinase 12) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)
|
BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • BARD1 mutation • BLM mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation • RAD51 mutation
almost2years
The impact of homologous recombination repair (HRR) gene mutation status on treatment (tx) patterns and clinical outcomes among patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) in the United States (US). (ASCO-GU 2023)
Chemotherapy was utilized in 43% of pts with HRRm vs 34% with HRRwt genes (P=0.40); docetaxel was the most common agent, utilized in 26% vs 27% of pts with HRRm vs HRRwt genes... In this rw study, genomic testing was performed frequently in later stages of metastatic disease. Pts with HRRm genes had numerically shorter rwPFS on 1L standard therapies compared with HRRwt pts. While unmet needs exist to optimize mCRPC txs and prolong disease progression irrespective of HRRm mutation status, further studies are warranted to further elucidate the prognostic role of HRRm and BRCA1/2 mutations on clinical outcomes.
Clinical • Clinical data • BRCA Biomarker • Metastases
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51C (RAD51 paralog C) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))
|
BRCA2 mutation • BRCA1 mutation • PALB2 mutation • CHEK2 mutation • RAD51C mutation • FANCA mutation • MRE11A mutation • NBN mutation
|
docetaxel
almost2years
Are Histological Patterns of Prostate Carcinoma Predictive of Homologous Recombination Deficiency Gene Mutations? (USCAP 2023)
In this study histological patterns were not predictive of HRD gene mutations. A marginal increase of neuroendocrine morphology and high-volume cribriform patterns were seen in BRCA1/2 and non- BRCA1/2 HRD mutated prostate carcinomas respectively. This data suggests that histopathologic examination alone is insufficient to distinguish BRCA1/2 and HRD gene mutated prostate cancers, further highlighting the importance of ancillary molecular diagnostics in therapy selection for those who may benefit from PARP inhibitors.
BRCA Biomarker • PARP Biomarker
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • EMSY (EMSY Transcriptional Repressor BRCA2 Interacting) • ABRAXAS1 (Abraxas 1 BRCA1 A Complex Subunit 2)
|
BRCA2 mutation • BRCA1 mutation • HRD • ATM mutation • PTEN mutation • PALB2 mutation • CHEK2 mutation • BRIP1 mutation • HRD + BRCA1 mutation • RAD51C mutation • RAD51D mutation • BARD1 mutation • MRE11A mutation • NBN mutation • CHEK1 expression
2years
SUKSES-B2: Olaparib and Bevacizumab in Relapsed Small Cell Lung Cancer Subjects (clinicaltrials.gov)
P2, N=28, Recruiting, Se-Hoon Lee | Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Dec 2022 --> Jun 2023
Trial completion date • Trial primary completion date • Combination therapy
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • SLFN11 (Schlafen Family Member 11) • BRCA (Breast cancer early onset) • RAD51 (RAD51 Homolog A) • RAD51B (RAD51 Paralog B) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • WRN (WRN RecQ Like Helicase) • POU2F3 (POU Class 2 Homeobox 3) • RAD52 (RAD52 Homolog DNA Repair Protein) • RECQL5 (RecQ Like Helicase 5) • RECQL (RecQ Like Helicase) • RECQL4( RecQ Like Helicase 4) • RPA1 (Replication Protein A1)
|
BRCA2 mutation • BRCA1 mutation • RAD51C mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • BLM mutation • BRCA mutation • MRE11A mutation • RAD54L mutation • NBN mutation • RAD52 mutation • RECQL mutation • RECQL4 mutation • RECQL5 mutation
|
Avastin (bevacizumab) • Lynparza (olaparib)
over2years
Mutation profiles in circulating cell-free DNA predict acquired resistance to Olaparib in high-grade serous ovarian carcinoma. (PubMed, Cancer Sci)
MRE11A:p.K464R may be a vital driving factor of Olaparib resistance, which patients who newly acquired MRE11A:p.K464R in post-treatment cfDNA had significantly shorter PFS than those without it. These findings provide potential noninvasive biomarkers for efficacy evaluation and resistance monitoring of Olaparib treatment, and lay the foundation for developing combination treatment after Olaparib resistance.
Preclinical • Journal • BRCA Biomarker • PARP Biomarker
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • MRE11A (MRE11 homolog, double strand break repair nuclease)
|
BRCA2 mutation • BRCA1 mutation • CHEK2 mutation • BRCA mutation • MRE11A mutation
|
Lynparza (olaparib)
over2years
CHANGEABLE: Combination of HX008 And Niraparib in GErm-line-mutAted Metastatic Breast Cancer (clinicaltrials.gov)
P2, N=37, Recruiting, Fudan University | Not yet recruiting --> Recruiting | Trial completion date: Apr 2022 --> Dec 2022 | Trial primary completion date: Feb 2022 --> Nov 2022
Enrollment open • Trial completion date • Trial primary completion date
|
HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • BAP1 (BRCA1 Associated Protein 1) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • WRN (WRN RecQ Like Helicase) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCC (FA Complementation Group C)
|
HER-2 positive • BRCA2 mutation • BRCA1 mutation • HR positive • HER-2 negative • ATM mutation • PALB2 mutation • CDK12 mutation • BAP1 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • HR positive + HER-2 negative • RAD50 mutation • BARD1 mutation • BLM mutation • CHEK1 mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation • CHEK1 expression
|
Herceptin (trastuzumab) • Zejula (niraparib) • Puyouheng (pucotenlimab)
over2years
New trial
|
TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • HOXB13 (Homeobox B13)
|
BRCA1 mutation • PTEN mutation • PALB2 mutation • BRIP1 mutation • MSH2 mutation • RAD51C mutation • RAD51D mutation • RAD50 mutation • BARD1 mutation • BLM mutation • MRE11A mutation • MLH3 mutation • NBN mutation
over2years
M6620 (VX-970) in Selected Solid Tumors (clinicaltrials.gov)
P2; Active, not recruiting --> Completed
Trial completion
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • ATM (ATM serine/threonine kinase) • ARID1A (AT-rich interaction domain 1A) • CCNE1 (Cyclin E1) • CDK12 (Cyclin dependent kinase 12) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • FANCC (FA Complementation Group C)
|
BRCA2 mutation • BRCA1 mutation • ATM mutation • ARID1A mutation • MYC amplification • CCNE1 amplification • CDK12 mutation • ATRX mutation • CHEK2 mutation • FBXW7 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation
|
OncoPanel™ Assay
|
berzosertib (M6620)
over2years
Pan-cancer analysis revealed characteristics of reversion mutations in homologous recombination repair genes (AACR 2022)
This study analyzed clinical and mutational characteristics of reversion mutations in HRR genes, which could occur as single or multiple variants to restore the function of predisposed pathogenic HRR mutations, resulting in resistance to platinum-based chemotherapies or PARP inhibitors. Monitoring these mutations with tissue or liquid biopsy samples are crucial for treatment guidance.
BRCA Biomarker • PARP Biomarker • Pan tumor
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • WRN (WRN RecQ Like Helicase) • FANCI (FA Complementation Group I) • ERCC3 (ERCC Excision Repair 3, TFIIH Core Complex Helicase Subunit) • FANCD2 (FA Complementation Group D2) • FANCC (FA Complementation Group C)
|
BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • BLM mutation • CHEK1 mutation • MRE11A mutation • RAD54L mutation • NBN mutation • WRN mutation • FANCI mutation • CHEK1 expression
almost3years
Mutations in DNA damage response pathways as a potential biomarker for immune checkpoint blockade efficacy: evidence from a seven-cancer immunotherapy cohort. (PubMed, Aging (Albany NY))
Mutations in DDR pathways or single DDR genes were associated with preferable ICB efficacy in specific cancers or subpopulations. Findings from our study would provide clues for tailing clinical trials and immunotherapy strategies.
Clinical • Journal • Checkpoint inhibition • Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker
|
TMB (Tumor Mutational Burden) • MSH2 (MutS Homolog 2) • MRE11A (MRE11 homolog, double strand break repair nuclease)
|
TMB-H • ATM mutation • MSH2 mutation • MRE11A mutation
almost3years
Niraparib in Tumors Metastatic to the CNS (clinicaltrials.gov)
P2, N=20, Recruiting, Massachusetts General Hospital | Not yet recruiting --> Recruiting
Enrollment open
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • BAP1 (BRCA1 Associated Protein 1) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • XRCC2 (X-Ray Repair Cross Complementing 2) • RAD54B (RAD54 Homolog B) • XRCC3 (X-Ray Repair Cross Complementing 3)
|
BRCA1 mutation • HRD • ATM mutation • PALB2 mutation • BAP1 mutation • BRIP1 mutation • HRD + BRCA1 mutation • RAD51C mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • BARD1 mutation • MRE11A mutation • RAD54L mutation • NBN mutation
|
Zejula (niraparib)
3years
Genomic Profiling Identified Copy Number Variations of CDK4/6 as a Novel Prognostic Biomarker for Thalamic Glioma (SNO 2021)
Gene enrichment analysis demonstrated that those genes were related to astrocyte differentiation. CONCLUSIONS In our study, CDK4/6 copy number variation was determined as a favorable overall survival biomarker for thalamic glioma, and CDK4/6 copy number variation associated mutant genes were related to astrocyte differentiation, which could be the potential therapeutic targets for thalamic glioma.
EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • TERT (Telomerase Reverse Transcriptase) • CDK4 (Cyclin-dependent kinase 4) • ATRX (ATRX Chromatin Remodeler) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • MUTYH (MutY homolog) • JARID2 (Jumonji And AT-Rich Interaction Domain Containing 2)
|
PTEN mutation • ROS1 positive • BRIP1 mutation • TERT mutation • MRE11A mutation
3years
Germline BRCA 1/2 and other predisposition genes in high-risk early-stage HR+/HER2- breast cancer (BC) patients treated with endocrine therapy (ET) with or without palbociclib: A secondary analysis from the PENELOPE-B study (SABCS 2021)
In this case-cohort analysis of 442 patients enrolled in the PENELOPE-B trial, the detection of BC predisposition genes was lower than expected with 10%. This is probably due to the low rate of g BRCA 1/2 carriers (3.4%), which could be influenced by the selection criteria of the trial. Patients with g BRCA 1/2 or other BC disposition genes had a comparable outcome to non-carriers in the PENELOPE-B trial.
Clinical • BRCA Biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • ATM (ATM serine/threonine kinase) • STK11 (Serine/threonine kinase 11) • PALB2 (Partner and localizer of BRCA2) • BRCA (Breast cancer early onset) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • XRCC2 (X-Ray Repair Cross Complementing 2) • FANCM (FA Complementation Group M)
|
BRCA2 mutation • BRCA1 mutation • HER-2 negative • PALB2 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD50 mutation • BARD1 mutation • BRCA mutation • MRE11A mutation • FANCM mutation • RAD51 mutation
|
Ibrance (palbociclib)
over3years
SUKSES-B2: Olaparib and Bevacizumab in Relapsed Small Cell Lung Cancer Subjects (clinicaltrials.gov)
P2, N=28, Recruiting, Se-Hoon Lee | Not yet recruiting --> Recruiting
Clinical • Enrollment open • Combination therapy
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • SLFN11 (Schlafen Family Member 11) • BRCA (Breast cancer early onset) • RAD51 (RAD51 Homolog A) • RAD51B (RAD51 Paralog B) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • WRN (WRN RecQ Like Helicase) • RAD52 (RAD52 Homolog DNA Repair Protein) • RECQL5 (RecQ Like Helicase 5) • RECQL (RecQ Like Helicase) • RECQL4( RecQ Like Helicase 4) • RPA1 (Replication Protein A1)
|
BRCA2 mutation • BRCA1 mutation • RAD51C mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • BLM mutation • BRCA mutation • MRE11A mutation • RAD54L mutation • NBN mutation • RAD52 mutation • RECQL mutation • RECQL4 mutation • RECQL5 mutation
|
Avastin (bevacizumab) • Lynparza (olaparib)
over3years
Niraparib in Tumors Metastatic to the CNS (clinicaltrials.gov)
P2, N=20, Not yet recruiting, Massachusetts General Hospital
New P2 trial
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • BAP1 (BRCA1 Associated Protein 1) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • XRCC2 (X-Ray Repair Cross Complementing 2)
|
BRCA1 mutation • HRD • ATM mutation • PALB2 mutation • BAP1 mutation • BRIP1 mutation • HRD + BRCA1 mutation • RAD51C mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • BARD1 mutation • MRE11A mutation • RAD54L mutation • NBN mutation
|
Zejula (niraparib)
over3years
MRN complex and cancer risk: old bottles, new wine. (PubMed, Clin Cancer Res)
Despite having their two-decade old candidacy as breast cancer genes close to being refuted, it has recently been reported that the MRN genes rise to have potential new roles in clonal hematopoiesis. In this article, we discuss the history and current status of MRN genes' clinical utility in breast cancer and then focus on their recently uncovered and less understood roles in clonal hematopoiesis that likely predispose to health-related disorders such as hematological malignancies and/or cardiovascular morbid events.
Journal • BRCA Biomarker
|
BRCA1 (Breast cancer 1, early onset) • RAD50 (RAD50 Double Strand Break Repair Protein) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))
|
RAD50 mutation • MRE11A mutation • NBN mutation
over3years
Clinical • New P2 trial • Combination therapy
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • SLFN11 (Schlafen Family Member 11) • BRCA (Breast cancer early onset) • RAD51 (RAD51 Homolog A) • RAD51B (RAD51 Paralog B) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • WRN (WRN RecQ Like Helicase) • RAD52 (RAD52 Homolog DNA Repair Protein) • RECQL5 (RecQ Like Helicase 5) • RECQL (RecQ Like Helicase) • RECQL4( RecQ Like Helicase 4) • RPA1 (Replication Protein A1)
|
BRCA2 mutation • BRCA1 mutation • RAD51C mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • BLM mutation • BRCA mutation • MRE11A mutation • RAD54L mutation • NBN mutation • RAD52 mutation • RECQL mutation • RECQL4 mutation • RECQL5 mutation
|
Avastin (bevacizumab) • Lynparza (olaparib)
over3years
[VIRTUAL] Pathological complete response rate and survival in patients with BRCA-associated triple-negative breast cancer after 12 weeks of de-escalated neoadjuvant chemotherapy: Translational results of the WSG-ADAPT TN randomized phase II trial (NCT01815242). (ASCO 2021)
Background: The phase II trial WSG-ADAPT TN randomized triple-negative breast cancer (TNBC) patients to receive 12 weeks of neoadjuvant nab-paclitaxel (nab-pac) combined with carboplatin (carbo) vs gemcitabine (gem) and showed a substantial improvement of pathological complete response (pCR: ypT0/is, ypN0) with carbo (45.9% vs 28.7%) . Twelve weeks of neoadjuvant nab-pac/carbo is a highly effective anthracycline-free regimen that leads to an excellent pCR-rate of 64% in tumor BRCA1/2-mutated cases . BRCA1/2 mutation status could support this de-escalation strategy in early TNBC, but further prospective validation of survival impacts in larger cohorts and with longer follow up is needed . More detailed survival analyses will be presented at the meeting.
Clinical • P2 data • BRCA Biomarker
|
TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • PALB2 (Partner and localizer of BRCA2) • BRCA (Breast cancer early onset) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • XRCC2 (X-Ray Repair Cross Complementing 2) • FANCM (FA Complementation Group M)
|
TP53 mutation • ATM mutation • PTEN deletion • PTEN mutation • STK11 mutation • PALB2 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD50 mutation • BARD1 mutation • BRCA mutation • MRE11A mutation • NBN mutation • FANCM mutation • RAD51 mutation
|
carboplatin • gemcitabine • albumin-bound paclitaxel
over3years
Biochemical and structural characterization of analogs of MRE11 breast cancer-associated mutant F237C. (PubMed, Sci Rep)
Moreover, by comparing the NMR data for this cancer-associated mutant with two previously described Mre11 separation-of-nuclease function mutants, a potential allosteric network was detected within Mre11 that connects the active site to regions responsible for recognizing the DNA ends and for dimerization. Together, our data further highlight the dynamics required for Mre11 nuclease function and illuminate the presence of allostery within the enzyme.
Journal
|
RAD50 (RAD50 Double Strand Break Repair Protein) • MRE11A (MRE11 homolog, double strand break repair nuclease)
|
MRE11A mutation
over3years
M6620 (VX-970) in Selected Solid Tumors (clinicaltrials.gov)
P2, N=30, Active, not recruiting, Massachusetts General Hospital | N=223 --> 30
Enrollment change
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • ATM (ATM serine/threonine kinase) • ARID1A (AT-rich interaction domain 1A) • CCNE1 (Cyclin E1) • CDK12 (Cyclin dependent kinase 12) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • FANCC (FA Complementation Group C)
|
BRCA2 mutation • BRCA1 mutation • ATM mutation • ARID1A mutation • MYC amplification • CCNE1 amplification • CDK12 mutation • ATRX mutation • CHEK2 mutation • FBXW7 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation
|
berzosertib (M6620)
almost4years
[VIRTUAL] Analysis of prognostic and predictive factors of response in squamous cell carcinoma using NGS techniques (ELCC 2021)
The samples were analyzed by NGS with the OncoDEEP (OncoDNA) panel covering 313 genes.ResultsOnly one of the cases was not evaluable due to the low cellularity of the tumor block. Of the 12 evaluable cases, molecular alterations were identified in 6 of them, as detailed below: in case number 1 (lung cancer) variant of TP53 cDNA c.595G> T-AA p. G199, in case number 2 (lung cancer) mutation in TP53 cDNA c.488a> G-AAp.Y163C and mutation in FANCA cDNA: c.3263C> T-AA: p.S1088F, in case number 3 (lung cancer) variant de TP53 c.DNA: c.455del-Aap.P152Rfs * 18, alteration in MRE11A cDNA: c.1688C> G-AA: p.S563 * and alteration KEAP1 cDNAc.224dup-Aap.L76Afs * 3, in case number 4 (lung cancer) AKT amplification and alteration in BRCA2 cDNA c.2701del-Aap.A902Lfs * 2, in case number 5 (lung cancer) mutation in PI3KCA E545 K, amplification in MDM2 and mutation in TP53 cDNA c.871AA> T-AA p.K291 *, in case number 6 (bladder cancer) amplification of JAK1 and in case number 7 (head and neck cancer) mutation of PI3KCA E545, mutation of TPMT Y240C and mutation in TPMT A154 T.Conclusions This review presents as its objective the analysis of these molecular alterations and their impact on the prognosis, and therapeutic evolution of patients with the aim of integrating clinical and molecular information in a translational oncology study
BRCA Biomarker • IO biomarker • Next-generation sequencing
|
TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • KEAP1 (Kelch Like ECH Associated Protein 1) • MDM2 (E3 ubiquitin protein ligase) • JAK1 (Janus Kinase 1) • FANCA (FA Complementation Group A) • MRE11A (MRE11 homolog, double strand break repair nuclease)
|
TP53 mutation • KEAP1 mutation • FANCA mutation • MDM2 mutation • MRE11A mutation
|
OncoDEEP
almost4years
SUKSES-B: Olaparib Monotherapy in Relapsed Small Cell Lung Cancer Patients With HR Pathway Gene Mutations Not Limited to BRCA 1/2 Mutations, ATM Deficiency or MRE11A Mutations (clinicaltrials.gov)
P2, N=15, Completed, Samsung Medical Center | Recruiting --> Completed | N=28 --> 15 | Trial completion date: Sep 2021 --> Jan 2021 | Trial primary completion date: Sep 2021 --> Jan 2021
Clinical • Trial completion • Enrollment change • Trial completion date • Trial primary completion date
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • RAD51 (RAD51 Homolog A) • RAD51B (RAD51 Paralog B) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • WRN (WRN RecQ Like Helicase) • RAD52 (RAD52 Homolog DNA Repair Protein) • RECQL5 (RecQ Like Helicase 5) • RECQL (RecQ Like Helicase) • RECQL4( RecQ Like Helicase 4) • RPA1 (Replication Protein A1)
|
BRCA2 mutation • BRCA1 mutation • RAD51C mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • BLM mutation • MRE11A mutation • RAD54L mutation • NBN mutation • WRN mutation • RAD52 mutation • RECQL mutation • RECQL4 mutation • RECQL5 mutation • RPA1 mutation
|
Lynparza (olaparib)
almost4years
M6620 (VX-970) in Selected Solid Tumors (clinicaltrials.gov)
P2, N=223, Active, not recruiting, Massachusetts General Hospital | Recruiting --> Active, not recruiting
Enrollment closed
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • ATM (ATM serine/threonine kinase) • ARID1A (AT-rich interaction domain 1A) • CCNE1 (Cyclin E1) • CDK12 (Cyclin dependent kinase 12) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • FANCC (FA Complementation Group C)
|
BRCA2 mutation • BRCA1 mutation • ATM mutation • ARID1A mutation • MYC amplification • CCNE1 amplification • CDK12 mutation • ATRX mutation • CHEK2 mutation • FBXW7 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation
|
berzosertib (M6620)
4years
Analysis of 11 candidate genes in 849 adult patients with suspected hereditary cancer predisposition. (PubMed, Genes Chromosomes Cancer)
No mutation was identified in RAD51, MRE11A, FAM175A, XRCC2, or MLH3. The involvement of these genes in the hereditary predisposition to cancer cannot be ruled out, although if it exists it is rare or does not seem to involve truncating variants.
Clinical • Journal
|
RAD51 (RAD51 Homolog A) • RAD51B (RAD51 Paralog B) • RAD50 (RAD50 Double Strand Break Repair Protein) • BARD1 (BRCA1 Associated RING Domain 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • PMS1 (PMS1 protein homolog 1) • FANCM (FA Complementation Group M)
|
RAD50 mutation • RAD51B mutation • BARD1 mutation • MRE11A mutation • MLH3 mutation • FANCM mutation • RAD51 mutation
4years
Pathogenic germline variants are associated with poor survival in stage III/IV melanoma patients. (PubMed, Sci Rep)
Integrative analysis showed germline mutation status conferred the highest risk (HR 5.2, 95% CI 1.72-15.7). Stage IV (HR 2.5, 0.74-8.6) and low TMB (HR 2.3, 0.57-9.4) were similar, whereas BRAF V600 status was the weakest prognostic biomarker (HR 1.5, 95% CI 0.44-5.2).
Clinical • Journal • Tumor Mutational Burden
|
BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDK4 (Cyclin-dependent kinase 4) • MRE11A (MRE11 homolog, double strand break repair nuclease) • RECQL4( RecQ Like Helicase 4)
|
BRAF V600E • BRAF mutation • BRAF V600 • ATM mutation • TMB-L • CDKN2A mutation • MRE11A mutation • RECQL4 mutation • CDK4 mutation
4years
[VIRTUAL] Comparison of genomic instability test scores used for predicting PARP activity in ovarian cancer (IGCS 2020)
Among patients with positive HRD scores, up to 51% were negative by %LOH and up to 63% were negative by the 11-gene panel. Only 3% of patients identified as positive by %LOH and 7% positive by the 11-gene panel were negative by HRD score. Conclusions/Implications: These data show that HR deficiency tests used in clinical trials are not equivalent and should not be considered interchangeable in predicting PARP inhibitor response in clinical practice.
BRCA Biomarker • PARP Biomarker
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • BARD1 (BRCA1 Associated RING Domain 1) • MRE11A (MRE11 homolog, double strand break repair nuclease)
|
ATM mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • BARD1 mutation • MRE11A mutation • NBN mutation
over4years
Clinical • New P2 trial • BRCA Biomarker • PARP Biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • BAP1 (BRCA1 Associated Protein 1) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • WRN (WRN RecQ Like Helicase) • FANCM (FA Complementation Group M) • FANCC (FA Complementation Group C)
|
HER-2 positive • BRCA2 mutation • BRCA1 mutation • HR positive • HER-2 negative • ATM mutation • PALB2 mutation • CDK12 mutation • BAP1 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • HR positive + HER-2 negative • RAD50 mutation • BARD1 mutation • BLM mutation • CHEK1 mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation • CHEK1 expression
|
Herceptin (trastuzumab) • Zejula (niraparib) • Puyouheng (pucotenlimab)
over4years
[VIRTUAL] Frequency of homologous recombination-related gene mutations in breast cancer and their correlation with tumor mutation burden (AACR-II 2020)
Our study revealed that HR-DDR mutations occurred in 38.1% of Chinese breast cancer patients, and BRCA2 was the most commonly mutated gene. HR-DDR mutations were associated with a higher TMB value, indicating a potential strategy for immunotherapy in Chinese breast cancer patients. The role of HRD-directed therapies, including poly-ADP ribose polymerase inhibitors and newer agents such as ATR inhibitors, needs to be explored.
Tumor Mutational Burden • BRCA Biomarker • PARP Biomarker • IO biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1) • PALB2 (Partner and localizer of BRCA2) • ATRX (ATRX Chromatin Remodeler) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • ATR (Ataxia telangiectasia and Rad3-related protein) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD50 (RAD50 Double Strand Break Repair Protein) • AURKA (Aurora kinase A) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • RAD54L (DNA Repair And Recombination Protein RAD54) • WRN (WRN RecQ Like Helicase)
|
BRCA2 mutation • BRCA1 mutation • ARID1A mutation • FANCA mutation • RAD50 mutation • CHEK1 mutation • MRE11A mutation • RAD54L mutation • CHEK1 expression
over4years
[VIRTUAL] Effect of genetic testing results on patient-reported quality of life among patients undergoing panel testing for newly diagnosed ovarian cancer. (ASCO 2020)
"A pathogenic result does not impact QoL scales immediately pre or post GT or at 6 months post GT, though patients with negative mutations were more likely to show a decrease in anxiety over time. Patients should be recommended GT at time of diagnosis of ovarian cancer without concern of increased stress, anxiety, or depression based on GT results. Research Funding: NYU Langone Health, Pharmaceutical/Biotech Company"
HEOR • Clinical
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSH2 (MutS Homolog 2) • MRE11A (MRE11 homolog, double strand break repair nuclease)
|
BRCA2 mutation • BRCA1 mutation • MSH2 mutation • MRE11A mutation