News - ATM mutation - LARVOL VERI

10d

CORONADO CLL: RP-3500 and Olaparib in DNA Damage Repair Pathway Deficient Relapsed/Refractory Chronic Lymphocytic Leukemia (clinicaltrials.gov)

P1/2, N=5, Terminated, University of Utah | N=39 --> 5 | Trial completion date: Aug 2027 --> Oct 2024 | Recruiting --> Terminated; This study was terminated due to sponsor de-activation of all programs associated with RP-3500 (camonsertib).

10 days ago

Enrollment change • Trial completion date • Trial termination

TP53 (Tumor protein P53) • BCL2 (B-cell CLL/lymphoma 2) • CD20 (Membrane Spanning 4-Domains A1) • SF3B1 (Splicing Factor 3b Subunit 1) • CCND1 (Cyclin D1) • CD5 (CD5 Molecule) • POT1 (Protection of telomeres 1) • FCER2 (Fc Fragment Of IgE Receptor II)

TP53 mutation • ATM mutation • Chr t(11;14) • SF3B1 mutation

Lynparza (olaparib) • camonsertib (RP-3500)

14d

Vascular Supply Identification, Lesion Extension and Search for Tumor Similarity at a Distance by VTM in Breast Cancer (clinicaltrials.gov)

P=N/A, N=120, Not yet recruiting, Galzu Institute of Research, Teaching, Science and Applied Technology | Trial completion date: Nov 2024 --> Nov 2025 | Trial primary completion date: Sep 2024 --> Jun 2025

14 days ago

Trial completion date • Trial primary completion date

TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • S100P (S100 calcium binding protein P)

BRCA1 mutation • ATM mutation • TP53 expression

15d

A Complete Response to Combined Immunotherapy in a Patient with an ATM plus SF3B1 Mutation and a Moderate Tumor Mutational Burden with a High-Grade Treatment-Emergent Neuroendocrine Prostate Cancer: Case Report and Review of the Literature. (PubMed, Case Rep Oncol)

We describe an impressive response to IO combination immunotherapy with ipilimumab plus nivolumab (Ipi/nivo) in a patient with T-NEPC who had failed standard treatment approaches. The results of the next-generation sequencing DNA analysis demonstrated the presence of intermediary tumor burden, an ATM mutation and a rare SF3B1 (G742D) mutation, and served as rational for IO therapy in this patient. This case highlights the genetic profile of tumor with a rare combination of ATM and SF3B1 mutations that could be further explored as biomarkers for IO therapy in T-NEPC and other tumor types.

15 days ago

Review • Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker

TMB (Tumor Mutational Burden) • ATM (ATM serine/threonine kinase) • SF3B1 (Splicing Factor 3b Subunit 1)

ATM mutation • SF3B1 mutation

Opdivo (nivolumab) • Yervoy (ipilimumab)

16d

Spatial immunogenomic patterns associated with lymph node metastasis in lung adenocarcinoma. (PubMed, Exp Hematol Oncol)

This study offers a comprehensive analysis of the genetic and immune profiles in LUAD primary tumors with LN metastasis, identifying key immunogenomic patterns linked to metastatic progression. The predictive model derived from these insights marks a substantial advancement in personalized treatment, underscoring its potential to improve patient management.

16 days ago

Journal

PIK3CG (Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Gamma)

ATM mutation

17d

GENTleMEN: Genetic Testing for Men With Metastatic Prostate Cancer (clinicaltrials.gov)

P=N/A, N=799, Active, not recruiting, University of Washington | Trial completion date: Aug 2024 --> Aug 2025

17 days ago

Trial completion date

BRCA1 (Breast cancer 1, early onset) • HRD (Homologous Recombination Deficiency)

BRCA1 mutation • HRD • ATM mutation

20d

A Translational Study of the ATR Inhibitor Berzosertib as Monotherapy in Four Molecularly Defined Cohorts of Advanced Solid Tumors. (PubMed, Clin Cancer Res)

Across cohorts, only SDH-mutant GIST patients experienced prolonged disease control. Despite evidence of target engagement, patients enrolled to all other cohorts had short PFS, suggesting rapid adaptation to ATR inhibitor monotherapy. Among these patients, those with tumors expressing SLFN11 during berzosertib exposure derived the most clinical benefit.

20 days ago

Journal • Metastases

ATM (ATM serine/threonine kinase) • SLFN11 (Schlafen Family Member 11) • ATRX (ATRX Chromatin Remodeler) • CHEK1 (Checkpoint kinase 1)

ATM mutation • ATRX mutation

berzosertib (M6620)

20d

CDX2-Suppressed Colorectal Cancers Possess Potentially Targetable Alterations in Receptor Tyrosine Kinases and Other Colorectal-Cancer-Associated Pathways. (PubMed, Diseases)

CDX2-suppressed colorectal cancers constitute a genomically distinct subset of colon and rectal cancers that have a lower prevalence of KRAS, APC, and TP53 mutations, but a high prevalence of mutations in less commonly mutated colorectal cancer genes. These alterations could serve as targets for personalized therapeutics in this subset.

20 days ago

Journal • BRCA Biomarker

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • APC (APC Regulator Of WNT Signaling Pathway) • ERBB4 (erb-b2 receptor tyrosine kinase 4) • CDX2 (Caudal Type Homeobox 2)

TP53 mutation • KRAS mutation • BRAF mutation • ATM mutation • APC mutation • ERBB3 mutation

24d

Niraparib in Patients With Pancreatic Cancer (clinicaltrials.gov)

P2, N=32, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Feb 2025 --> Feb 2026 | Trial primary completion date: Sep 2024 --> Sep 2025

24 days ago

Trial completion date • Trial primary completion date

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • CHEK2 (Checkpoint kinase 2)

BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CHEK2 mutation

Zejula (niraparib)

25d

Cohort Study of Pancreatic Cancer Risk (clinicaltrials.gov)

P=N/A, N=419, Active, not recruiting, Mayo Clinic | N=2000 --> 419

25 days ago

Enrollment change

TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • APC (APC Regulator Of WNT Signaling Pathway) • EPCAM (Epithelial cell adhesion molecule)

TP53 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • APC mutation • MSH2 mutation • PMS2 mutation

27d

Somatic gene mutations involved in DNA damage response/Fanconi anemia signaling are tissue- and cell-type specific in human solid tumors. (PubMed, Front Med (Lausanne))

Furthermore, these gene alteration patterns significantly impact patient survival and disease-free periods. Collectively, our findings not only enhance our understanding of cancer development and progression but also have significant implications for cancer patient care and prognosis, particularly in the development of effective therapeutic strategies.

27 days ago

Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • FANCF (FA complementation group F) • FANCL (FA Complementation Group L) • XRCC2 (X-Ray Repair Cross Complementing 2) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit) • FANCI (FA Complementation Group I) • FANCM (FA Complementation Group M) • MAD2L2 (Mitotic Arrest Deficient 2 Like 2) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCG (FA Complementation Group G) • FAAP24 (FA Core Complex Associated Protein 24) • FANCB (FA Complementation Group B) • FANCC (FA Complementation Group C) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)

ATM mutation

29d

Molecular and Clinical Features of Pancreatic Acinar Cell Carcinoma: A Single-Institution Case Series. (PubMed, Cancers (Basel))

One patient was found to have RET fusion and responded favorably to selpercatinib for over 42 months...One of the additional two cases who underwent BostonGene testing was found to have NTRK1 fusion. RNA and TME analysis by Boston Gene of the two cases reported immune desert features and relatively lower RNA levels of CEACAM5, CD47, CD74, and MMP1 and higher RNA levels of CDH6 compared with PDAC.

29 days ago

Journal • BRCA Biomarker

KRAS (KRAS proto-oncogene GTPase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RET (Ret Proto-Oncogene) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • CD74 (CD74 Molecule) • PALB2 (Partner and localizer of BRCA2) • CEACAM5 (CEA Cell Adhesion Molecule 5) • CDH6 (Cadherin 6) • MMP1 (Matrix metallopeptidase 1)

BRCA2 mutation • BRCA1 mutation • NTRK1 fusion • RET fusion • ATM mutation • PALB2 mutation • KRAS wild-type

Retevmo (selpercatinib)

Mutational analysis differentiating sporadic carcinomas from colitis-associated colorectal carcinomas. (PubMed, Cell Commun Signal)

Taken together, our data highlights genetic differences between sCRC and CAC and enables the possibility to utilize specific gene alterations to support the pathologist's diagnosis.

1 month ago

Journal

KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)

KRAS mutation • PIK3CA mutation • KRAS G12D • ATM mutation • KRAS G12

Understanding genetic variations associated with familial breast cancer. (PubMed, World J Surg Oncol)

Familial breast cancer has been linked to several genetic diseases and mutations, according to studies. Screening for genetic disorders is recommended by National Comprehensive Cancer Network recommendations. Evaluation of breast cancer candidate variations and risk loci may improve individual risk assessment. Only high- and moderate-risk gene variations have clinical guidelines, whereas low-risk gene variants require additional investigation. With increasing use of NGS technology, more linkage with rare genes is being discovered.

1 month ago

Review • Journal • BRCA Biomarker

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) • PALB2 (Partner and localizer of BRCA2) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1)

ATM mutation • PALB2 mutation • CHEK2 mutation • BRIP1 mutation

Double Hit in Clear-Cell Renal Cell Carcinoma With Germline Pathogenic ATM Mutation and Somatic VHL Mutation. (PubMed, J Investig Med High Impact Case Rep)

This case highlights the potential use for enhanced screening protocols for RCC in patients who have germline pathogenic ATM mutations and the importance of research in targeted treatments for tumors driven by dual genetic mechanisms. Increased awareness and vigilant screening for RCC are crucial in managing hereditary cancer syndromes effectively.

1 month ago

Journal • BRCA Biomarker

TP53 (Tumor protein P53) • ATM (ATM serine/threonine kinase) • VHL (von Hippel-Lindau tumor suppressor) • BRCA (Breast cancer early onset)

TP53 mutation • ATM mutation • VHL mutation • BRCA mutation

CHARACTERIZATION OF GENETIC ANCESTRY IN WOMEN DIAGNOSED WITH TRIPLE NEGATIVE BREAST AND HIGH-GRADE SEROSOUS OVARIAN CANCER, HEREDITARY/SPORADIC: IMPLEMENTATION OF A DIAGNOSTIC PANEL (IGCS 2024)

116 patients with a confirmatory primary diagnosis of TNBC (N= 75) and HGSOC (N= 41) were included. A higher Native American ancestry (NAM) proportion was observed in the hereditary group across the cohort (58% vs 45.2%). Among TNBC patients, hereditary cases exhibited a higher NAM ancestry mean (0.50 (SD, 0.14)).

1 month ago

Clinical • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • PMS2 (PMS1 protein homolog 2) • CDH1 (Cadherin 1)

BRCA2 mutation • BRCA1 mutation • ATM mutation • PMS2 mutation • CDH1 mutation

TruSight Hereditary Cancer Panel

Synchronous Pancreatic Ductal Adenocarcinoma and Nasopharyngeal Carcinoma With Associated Novel Pathogenic ATM Mutation. (PubMed, Anticancer Res)

To the best of our knowledge, this is the first documented case of synchronous PDAC and NPC in a patient with novel associated pathogenic ATM c.8545C>T (p.Arg2849*) mutation and poor prognosis. More similar case reports are needed to further characterize this entity.

1 month ago

Journal

ATM (ATM serine/threonine kinase)

ATM mutation

gemcitabine • 5-fluorouracil • albumin-bound paclitaxel • oxaliplatin • irinotecan • leucovorin calcium

2ms

Somatic mutation of targeted sequencing identifies risk stratification in advanced ovarian clear cell carcinoma. (PubMed, Gynecol Oncol)

Mutations in genes, including MUC16, ATM, NOTCH3, KMT2A, and CTNNA1, were associated with the poor prognosis of advanced OCCC. The risk stratification according to these genes demonstrated acceptable prediction power of prognosis and platinum response, suggesting the potential to be a novel target for precision medicine.

2 months ago

Journal • Metastases

KMT2A (Lysine Methyltransferase 2A) • MUC16 (Mucin 16, Cell Surface Associated) • NOTCH3 (Notch Receptor 3) • CTNNA1 (Catenin Alpha 1)

ATM mutation • MUC16 mutation • NOTCH3 mutation

2ms

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

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

2 months 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)

2ms

Histopathologic and Molecular Characterization of IDH-Mutant Prostatic Adenocarcinoma. (PubMed, Mod Pathol)

Our findings provide evidence that IDH1 hotspot mutations serve as driver alterations in this rare yet distinct molecular subset of PCa. Further studies are warranted to correlate response to androgen deprivation and IDH inhibitors.

2 months ago

Journal • BRCA Biomarker • MSi-H Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • RB1 (RB Transcriptional Corepressor 1) • ERG (ETS Transcription Factor ERG) • SPOP (Speckle Type BTB/POZ Protein) • TMPRSS2 (Transmembrane serine protease 2) • NKX3-1 (NK3 homeobox 1)

BRCA2 mutation • BRCA1 mutation • MSI-H/dMMR • IDH1 mutation • IDH2 mutation • ATM mutation • AR amplification • SPOP mutation • IDH1 R132 • IDH2 R140 • IDH2 R172

2ms

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

2 months 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

2ms

Comprehensive genetic analysis by targeted sequencing identifies risk factors and predicts patient outcome in Mantle Cell Lymphoma: results from the EU-MCL network trials. (PubMed, Leukemia)

Genetic complexity (≥3 CNVs) observed in 51% of analysed patients was significantly associated with impaired FFS and OS. We demonstrate that targeted sequencing from peripheral blood and bone marrow reliably detects diagnostically and prognostically important genetic factors in MCL patients, facilitating genetic characterization in clinical routine.

2 months ago

Journal

TP53 (Tumor protein P53) • ATM (ATM serine/threonine kinase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • RB1 (RB Transcriptional Corepressor 1) • CCND1 (Cyclin D1) • CXCR4 (Chemokine (C-X-C motif) receptor 4) • KMT2D (Lysine Methyltransferase 2D) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • BIRC3 (Baculoviral IAP repeat containing 3) • NFKBIE (NFKB Inhibitor Epsilon)

TP53 mutation • ATM mutation • CDKN2A deletion

2ms

The Potential for Targeting G2/M Cell Cycle Checkpoint Kinases in Enhancing the Efficacy of Radiotherapy. (PubMed, Cancers (Basel))

Therefore, targeting the G2/M checkpoint through specific inhibitors is considered an important strategy for enhancing the efficacy of radiotherapy. In this review, we focus on inhibitors of Chk1 and Wee1 kinases and present the current biological evidence supporting their utility as radiosensitisers with different radiotherapy modalities, as well as clinical trials that have and are investigating their potential for cancer patient benefit.

2 months ago

Review • Journal

TP53 (Tumor protein P53) • CHEK1 (Checkpoint kinase 1)

TP53 mutation • ATM mutation

2ms

Rapid Remission With Upadacitinib in a Child With Refractory Crohn's Disease and ATM Mutation: A Case Report. (PubMed, Curr Ther Res Clin Exp)

This case report delineates successful remission with upadacitinib in a child with CD refractory to infliximab, ustekinumab, adalimumab, thalidomide, and prednisone. Notably, the patient carried an ataxia telangiectasia mutated (ATM) gene mutation. These findings provide valuable evidence for PCD management and highlight the potential benefits of upadacitinib in this population.

2 months ago

Journal

ATM (ATM serine/threonine kinase) • TNFA (Tumor Necrosis Factor-Alpha)

ATM mutation

prednisone • thalidomide

2ms

Circulating Tumor DNA (ctDNA) Monitoring in the Assessment and Prediction of the Efficacy of PARP Inhibitors (PARPi) (clinicaltrials.gov)

P=N/A, N=30, Recruiting, Sun Yat-sen University | Trial completion date: Aug 2023 --> Aug 2025

2 months ago

Trial completion date • Circulating tumor DNA

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • 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) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)

BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • RAD54L mutation • BRCA1 mutation + ATM mutation • CHEK1 expression

4ms

Reciprocal DNA Fusions and their Association with DNA Damage Response Genes in Patients with NSCLC Through cfDNA NGS (IASLC-WCLC 2024)

Notably, individuals with exclusive reciprocal rearrangements of RET or ROS1 might be less prone to co-mutations in TP53, ATM, and ARID1A, than are those with detectable activating rearrangements. This emphasizes the significance of evaluating co-mutations in DNA repair genes alongside fusions to refine treatment approaches.

4 months ago

Clinical • BRCA Biomarker • Next-generation sequencing • Cell-free DNA

ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • EML4 (EMAP Like 4) • ARID1A (AT-rich interaction domain 1A) • MLH1 (MutL homolog 1)

TP53 mutation • BRCA1 mutation • ATM mutation • ALK rearrangement • ARID1A mutation • ALK fusion • ROS1 rearrangement • RET rearrangement

Guardant360® CDx

4ms

Clonal haematopoiesis of indeterminate potential (CHIP) might mislead interpretation of ATM and CHEK2 alterations detected on liquid biopsies (ESMO 2024)

CHIP was highly prevalent in cancer patients likely due to genotoxic stress and ageing. The rate of mutations was dependant on cancer types and treatment context. The prevalence of mutated DNA repair genes CHEK2 and ATM was increased post-cisplatin exposure.

4 months ago

PARP Biomarker • Liquid biopsy • Biopsy

ATM (ATM serine/threonine kinase) • DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • TET2 (Tet Methylcytosine Dioxygenase 2) • CHEK2 (Checkpoint kinase 2)

ATM mutation • CHEK2 mutation

FoundationOne® Liquid CDx

cisplatin

6ms

A comprehensive analysis of POLE/POLD1 genomic alterations in colorectal cancer. (PubMed, Oncologist)

Patients with POLE/POLD1 mutations exhibited significant differences across immunological markers (ie, TMB, MMR, and MSI-H) and molecular co-alterations. Those with short variant mutations represented 18% of the POLE/POLD1 cohort and 0.4% of the total cohort examined. This group of patients had a median TMB of 159 mut/Mb (range 34-488), representing the ultra-hypermutated phenotype. This group of patients is important to identify given the potential for exceptional response to immune checkpoint inhibitors.

6 months ago

Journal • Tumor mutational burden • MSi-H Biomarker • BRCA Biomarker • IO biomarker

ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • RET (Ret Proto-Oncogene) • POLE (DNA Polymerase Epsilon) • POLD1 (DNA Polymerase Delta 1)

TMB-H • MSI-H/dMMR • ATM mutation • POLE mutation • ALK mutation • RET mutation • POLD1 mutation • POLE mutation + POLD1 mutation

Tempus xT Assay

6ms

Prospective Study of Homologous Recombination Repair Gene Mutation Prevalence in Patients With Advanced Prostate Cancer From Latin America: Challenges and Future Approaches. (PubMed, JCO Precis Oncol)

Despite the study's limitations, to our knowledge, PROSPECT was the first attempt to describe the prevalence of HRRm in patients with PC from LAC. Notably, the germline HRRm prevalence in this study was inferior to that observed in North American and European populations. The somatic HRR testing barriers identified are being addressed by several projects to improve access to HRR testing and biomarker-based therapies in LAC.

6 months ago

Clinical • Journal • BRCA Biomarker • Metastases

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • MRE11A (MRE11 homolog, double strand break repair nuclease)

ATM mutation • CHEK2 mutation • BRIP1 mutation • RAD51B mutation

6ms

Molecular characteristics of early-onset compared with late-onset colorectal cancer: A case controlled study. (PubMed, Int J Surg)

This study revealed a significantly higher MSI-H distribution rate in early-onset colorectal cancer, and EOCRC exhibits a distinct mutational signature coupled with higher PD-L1 expression. These findings hold promise in guiding personalized therapeutic strategies for improved disease management in EOCRC patients.

6 months ago

Journal • Tumor mutational burden • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • ARID1A (AT-rich interaction domain 1A) • PBRM1 (Polybromo 1) • LRP1B (LDL Receptor Related Protein 1B) • RNF43 (Ring Finger Protein 43) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • FAT1 (FAT atypical cadherin 1) • CASP8 (Caspase 8) • FANCI (FA Complementation Group I) • KMT2B (Lysine Methyltransferase 2B) • DPYD (Dihydropyrimidine Dehydrogenase)

PD-L1 expression • MSI-H/dMMR • ATM mutation • ARID1A mutation • PBRM1 mutation • RNF43 mutation • KMT2B mutation • FANCI mutation

6ms

GENTleMEN: Genetic Testing for Men With Metastatic Prostate Cancer (clinicaltrials.gov)

P=N/A, N=799, Active, not recruiting, University of Washington | N=2000 --> 799

6 months ago

Enrollment change • Metastases

BRCA1 (Breast cancer 1, early onset) • HRD (Homologous Recombination Deficiency)

BRCA1 mutation • HRD • ATM mutation

6ms

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.

6 months ago

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)

6ms

Columnar Cell Thyroid Carcinoma: A Heterogeneous Entity Demonstrating Overlap Between Papillary Thyroid Carcinoma and Follicular Neoplasms. (PubMed, Head Neck Pathol)

This study represents the largest molecularly defined cohort of non-oncocytic thyroid carcinomas with columnar cell morphology. These tumors represent a genetically and behaviorally heterogeneous group of neoplasms, some of which have RAS-like or follicular neoplasm-like genetics, some of which have BRAF-p.V600E-like or classic papillary thyroid carcinoma-like genetics, and some of which remain unclear. Noninvasive or minimally invasive tumors showed an indolent course compared to those with angioinvasion, gross extrathyroidal growth, or high-grade morphology. Consideration could be given to reclassification of this neoplasm outside of the subtyping of papillary thyroid carcinoma in light of its genetic diversity, distinct morphology, and clinical behavior more closely aligned with follicular thyroid neoplasms.

6 months ago

Journal

BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • NOTCH1 (Notch 1) • TERT (Telomerase Reverse Transcriptase) • NF2 (Neurofibromin 2) • RAS (Rat Sarcoma Virus) • AGK (Acylglycerol Kinase) • CDX2 (Caudal Type Homeobox 2)

BRAF V600E • BRAF V600 • ATM mutation • BRAF fusion • AGK-BRAF fusion • TERT mutation

6ms

Comprehensive Analysis of Predictors of the Treatment With Pembrolizumab and Olaparib in Patients With Unresectable or Metastatic HER2 Negative Breast Cancer and a Deleterious Germline Mutation or a Homologous Recombination Deficiency (COMPRENDO (clinicaltrials.gov)

P2, N=11, Active, not recruiting, Institut fuer Frauengesundheit | Recruiting --> Active, not recruiting | N=89 --> 11 | Trial primary completion date: Jan 2024 --> Jan 2025

6 months ago

Enrollment closed • Enrollment change • Trial primary completion date • Metastases

HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • XRCC2 (X-Ray Repair Cross Complementing 2) • FANCC (FA Complementation Group C) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)

BRCA2 mutation • BRCA1 mutation • HER-2 amplification • HER-2 negative • HRD • ATM mutation • PALB2 mutation • ER positive + PGR positive • CHEK2 mutation • PGR positive • RAD51C mutation • RAD51D mutation • BARD1 mutation • RAD51 mutation

Keytruda (pembrolizumab) • Lynparza (olaparib)

7ms

Absence of ATM leads to altered NK cell function in mice. (PubMed, Clin Immunol)

Results also suggest that expansion of exhausted NKG2D+ NK cells in Atm-/- mice is driven by low-level expression of stress-inducible NKG2D ligands, whereas development of thymoma expressing the high-affinity MULT1 ligand is associated with NKG2D down-regulation on NK cells. These results expand our understanding of immunodeficiency in A-T and encourage exploring NK cell biology in A-T patients in the attempt to identify cancer predictive biomarkers and novel therapeutic targets.

7 months ago

Preclinical • Journal

TNFA (Tumor Necrosis Factor-Alpha) • NKG2D (killer cell lectin like receptor K1)

ATM mutation • ATM expression

7ms

Ataxia Telengectesia Protein Influences Bleomycin-Induced DNA Damage in Human Fibroblast Cells. (PubMed, Cell Biochem Biophys)

These findings suggest that the genetic makeup of the cellular genome would play an essential role in repairing bleomycin-induced DNA damage. Signalling of DNA damage, and the genes responsible for the repair process, could contribute to the differential susceptibility of different tissues to carcinomas induced by environmental mutagens.

7 months ago

Journal

ATM (ATM serine/threonine kinase)

ATM mutation

bleomycin

7ms

DNA Checkpoint Gene Mutation as a Biomarker for Immune Checkpoint Inhibitor Therapy in Advanced Biliary Tract Cancer. (PubMed, Anticancer Res)

The DNACHK pathway is expected to serve as a potential biomarker for ICI treatment.

7 months ago

Journal • Checkpoint inhibition • BRCA Biomarker • IO biomarker • Metastases

TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • ATM (ATM serine/threonine kinase) • CHEK2 (Checkpoint kinase 2) • CHEK1 (Checkpoint kinase 1) • TP53BP1 (Tumor Protein P53 Binding Protein 1)

ATM mutation

7ms

Genomic Correlates of Prostate-Specific Membrane Antigen Expression and Response to 177Lu-PSMA-617: A Retrospective Multicenter Cohort Study. (PubMed, JCO Precis Oncol)

Outcomes on LuPSMA varied on the basis of mutational profile. Prospective studies to define the clinical activity of LuPSMA in predefined genomic subgroups are justified.

7 months ago

Retrospective data • Journal

TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • ATM (ATM serine/threonine kinase) • RB1 (RB Transcriptional Corepressor 1)

TP53 mutation • ATM mutation • PTEN mutation • RB1 mutation

Pluvicto (lutetium Lu 177 vipivotide tetraxetan)

7ms

Case report: Mutation evolution in a patient with TdT positive high grade B cell lymphoma with MYC and BCL2 rearrangements following the treatment of concurrent follicular lymphoma and diffuse large B-cell lymphoma. (PubMed, Discov Oncol)

This study reports a rare case of TdT positive "double hit" HGBL following the treatment of concurrent FL/DLBCL and highlights the mutation characteristics. Collectively, this study will help enrich the knowledge of TdT positive "double hit" HGBL transformed from FL/DLBCL.

7 months ago

Journal • IO biomarker

BCL2 (B-cell CLL/lymphoma 2) • FGFR3 (Fibroblast growth factor receptor 3) • CD20 (Membrane Spanning 4-Domains A1) • KMT2D (Lysine Methyltransferase 2D) • CHEK2 (Checkpoint kinase 2) • CREBBP (CREB binding protein) • BCL7A (BAF Chromatin Remodeling Complex Subunit BCL7A) • CCND3 (Cyclin D3) • MME (Membrane Metalloendopeptidase) • MUC4 (Mucin 4, Cell Surface Associated) • STAT6 (Signal transducer and activator of transcription 6) • ARID5B (AT-Rich Interaction Domain 5B) • DDX3X (DEAD-Box Helicase 3 X-Linked)

ATM mutation • MYC rearrangement + BCL2 rearrangement • KMT2D mutation • CHEK2 mutation • BCL2 expression • CD20 expression • MYC rearrangement • CD19 expression • BCL2 rearrangement • IGH translocation • BCL2 translocation

7ms

Prognostic impact of genetic abnormalities in 536 first-line chronic lymphocytic leukaemia patients without 17p deletion treated with chemoimmunotherapy in two prospective trials: Focus on IGHV-mutated subgroups (a FILO study). (PubMed, Br J Haematol)

Our findings highlight the diverse prognostic influence of genetic aberrations depending on the IGHV status in symptomatic CLL patients receiving first-line CIT. The prognosis of gene mutations and cytogenetic abnormalities needs to be investigated with a compartmentalized methodology, taking into account the IGVH status of patients receiving first-line BTK and/or BCL2 inhibitors.

7 months ago

Journal • IO biomarker

TP53 (Tumor protein P53) • ATM (ATM serine/threonine kinase) • SF3B1 (Splicing Factor 3b Subunit 1) • IGH (Immunoglobulin Heavy Locus) • SAMHD1 (SAM And HD Domain Containing Deoxynucleoside Triphosphate Triphosphohydrolase 1)

TP53 mutation • ATM mutation • Chr del(11q) • IGH mutation • SAMHD1 mutation

7ms

Treatment Patterns and Clinical Outcomes Among Patients With Metastatic Prostate Cancer Harboring Homologous Recombination Repair Mutations. (PubMed, Clin Genitourin Cancer)

Treatment patterns identified in this study were similar to those among patients with mCRPC regardless of tumor HRR mutation status in the literature.

7 months ago

Clinical data • Journal • BRCA Biomarker • Metastases

BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12)

ATM mutation • CDK12 mutation

7ms

KNIGHTS: High-Risk Metachronous Oligometastatic Prostate Cancer Trial (clinicaltrials.gov)

P2, N=88, Recruiting, University of Maryland, Baltimore | Not yet recruiting --> Recruiting

7 months ago

Enrollment open • Metastases

TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • RAD54L (DNA Repair And Recombination Protein RAD54)

BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • FANCA mutation

Zejula (niraparib) • abiraterone acetate • prednisone

7ms

Studying the Safety and Determining the Optimal Dose of Novobiocin in Patients With Tumors That Have Alterations in DNA Repair Genes (clinicaltrials.gov)

P1, N=30, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting

7 months ago

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