News - NBN mutation - LARVOL VERI

11ms

An exceptionally rare case of a diffuse midline glioma with concomitant H3.1 K27M and G34R mutations in the HIST1H3C (H3C3) gene. (PubMed, Acta Neuropathol Commun)

The patient was treated with adjuvant radiotherapy, but progressed and passed away 13 months post-diagnosis. This case is an exceptionally rare, complex variant of histone-mutant paediatric HGG, illustrating that the H3.1 K27M mutation demonstrates a dominance over the molecular and clinical profiles compared to G34R, and highlights the importance of broad molecular profiling to identify such examples for further study.

11 months ago

Journal

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • H3C1 (H3 Clustered Histone 1) • OLIG2 (Oligodendrocyte Transcription Factor 2)

PIK3CA mutation • NBN mutation

12ms

Alterations in DNA Damage Repair Genes Before and After Neoadjuvant Cisplatin-based Chemotherapy in Muscle-invasive Bladder Cancer. (PubMed, Eur Urol Open Sci)

Patients with muscle-invasive bladder cancer who have mutations in genes that are involved in repair of DNA damage are more likely to respond to cisplatin-based chemotherapy. Testing to identify these gene mutations could help in selecting the patients who are most likely to benefit from this treatment.

12 months ago

Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MLH1 (MutL homolog 1) • CDK12 (Cyclin dependent kinase 12) • ERCC2 (Excision repair cross-complementation group 2) • MSH3 (MutS Homolog 3) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • REV3L (REV3 Like DNA Directed Polymerase Zeta Catalytic Subunit) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)

CDK12 mutation • NBN mutation

cisplatin

12ms

High- and Moderate-Risk Variants Among Breast Cancer Patients and Healthy Donors Enrolled in Multigene Panel Testing in a Population of Central Russia. (PubMed, Int J Mol Sci)

The BLM, NBN, and MUTYH genes did not demonstrate associations with BC risk. Finding deleterious mutations in BC patients is important for diagnosis and management; in controls, it opens up the possibility of prevention and early diagnostics.

12 months ago

Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • MUTYH (MutY homolog) • XRCC2 (X-Ray Repair Cross Complementing 2)

PALB2 mutation • RAD51C mutation • RAD50 mutation • BARD1 mutation • BLM mutation • NBN mutation

12ms

Niraparib in Tumors Metastatic to the CNS (clinicaltrials.gov)

P2, N=20, Recruiting, Massachusetts General Hospital | Trial completion date: Dec 2026 --> Jun 2027 | Trial primary completion date: Dec 2024 --> Dec 2025

12 months ago

Trial completion date • Trial primary completion date • Metastases

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 • HRD signature

Zejula (niraparib)

1year

TRIUMPH: Trial of Rucaparib in Patients With Metastatic Hormone-Sensitive Prostate Cancer Harboring Germline DNA Repair Gene Mutations (clinicaltrials.gov)

P2, N=12, Completed, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Active, not recruiting --> Completed | N=30 --> 12

1 year ago

Trial completion • Enrollment change • Metastases

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCL (FA Complementation Group L) • FANCI (FA Complementation Group I) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCG (FA Complementation Group G) • FANCB (FA Complementation Group B) • FANCC (FA Complementation Group C)

CHEK2 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD50 mutation • FANCF mutation • NBN mutation • FANCG mutation • FANCI mutation • FANCM mutation

Rubraca (rucaparib)

1year

PROGRESS: Prostate Cancer Genetic Risk Evaluation and Screening Study (clinicaltrials.gov)

P=N/A, N=400, Recruiting, Massachusetts General Hospital | N=200 --> 400

1 year ago

Enrollment change

TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • EPCAM (Epithelial cell adhesion molecule) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • GEN1 (GEN1 Holliday junction 5' flap endonuclease) • HOXB13 (Homeobox B13)

CHEK2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • PMS2 mutation • NBN mutation

1year

CHANGEABLE: Combination of HX008 And Niraparib in GErm-line-mutAted Metastatic Breast Cancer (clinicaltrials.gov)

P2, N=37, Completed, Fudan University | Recruiting --> Completed

1 year ago

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)

1year

Acolbifene Versus Low Dose Tamoxifen for the Prevention of Breast Cancer in Premenopausal Women at High Risk for Development of Breast Cancer (clinicaltrials.gov)

P2, N=80, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting | Trial primary completion date: Sep 2026 --> Aug 2027

1 year ago

Enrollment open • Trial primary completion date

TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • ATM (ATM serine/threonine kinase) • NF1 (Neurofibromin 1) • MSH6 (MutS homolog 6) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2) • 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)) • AGR2 (Anterior gradient 2)

TP53 mutation • ATM mutation • PTEN mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • PMS2 mutation • BARD1 mutation • NBN mutation

tamoxifen • acolbifene

1year

Long-Term Survivor of Intrahepatic Cholangiocarcinoma for over 18 Years: Case Study with Longitudinal Histo-molecular and Tumor Immune Microenvironment Characterization and Systematic Review of the Literature. (PubMed, J Gastrointest Cancer)

This case study highlights the essential role of a stringent follow-up after resection of intrahepatic cholangiocarcinoma for detecting early relapsing tumors. Moreover, it shows the importance of the molecular characterization of multiple tumors for understanding their real nature. The accurate study of long-surviving patients highlights the features that are critical for outcome improvement.

1 year ago

Review • Journal

NOTCH3 (Notch Receptor 3) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))

NOTCH3 mutation • NBN mutation

over1year

Sequential ctDNA profiling in patients with advanced non-small cell lung cancer: An interim analysis of the COPE randomized study (ESMO 2024)

This study highlights serial ctDNA profiling's benefits for managing advanced NSCLC, providing real-time genetic data. It offers predictive insights as potential imaging substitutes, enables dynamic treatment adjustments, and identifies resistance to therapies.

over 1 year ago

Clinical • Circulating tumor DNA • Metastases

KRAS (KRAS proto-oncogene GTPase) • STK11 (Serine/threonine kinase 11) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • RB1 (RB Transcriptional Corepressor 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • STAG2 (Stromal Antigen 2) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))

STK11 mutation • STAG2 mutation • NBN mutation

FoundationOne® CDx • FoundationOne® Liquid CDx

over1year

Somatic structural variants drive distinct modes of oncogenesis in melanoma. (PubMed, J Clin Invest)

Experimental knockouts of MRE11 and NBN, followed by olaparib cell viability assays in melanoma cells, indicated that dysregulation of each of these genes may cause sensitivity to PARPi in cutaneous melanomas. Broadly, harmonized analysis of melanoma SVs revealed distinct global genomic properties and molecular drivers, which may have biological and therapeutic impact.

over 1 year ago

Journal • PARP Biomarker

MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))

NBN mutation

Lynparza (olaparib)

over1year

Outcomes of a universal germline screening program in a community urology practice. (PubMed, Clin Genet)

Genetic risk assessment for high-risk individuals is feasible as part of a universal screening program in a community urology practice. Approximately 8% of tested patients were found to have pathogenic germline mutations, which is consistent with contemporary tertiary referral cohorts.

over 1 year ago

Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CHEK2 (Checkpoint kinase 2) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))

BRCA2 mutation • BRCA1 mutation • CHEK2 mutation • NBN mutation

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