News - ATM mutation - LARVOL VERI

PIK3CA Mutations and Co-Mutations in Operated Non-Small Cell Lung Carcinoma. (PubMed, J Clin Med)

The top 10 mutations that most commonly accompanied PIK3CA variations were KRAS, NF1, TP53, EGFR, PTEN, BRAF, KIT, CDKN2A, SMARCA4, and ATM mutations, respectively. PIK3CA variations, along with other gene variations, may influence cancer progression and thus may play a crucial role in the determination of targeted treatment strategies.

5 days ago

Journal

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • 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) • ATM (ATM serine/threonine kinase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)

TP53 mutation • KRAS mutation • BRAF mutation • PIK3CA mutation • ATM mutation • PIK3CA H1047R • PTEN mutation • PIK3CA E545K • CDKN2A mutation • SMARCA4 mutation • PIK3CA E545 • PIK3CA E542

Phase II Trial of Risk-Enabled Therapy After Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer (RETAIN 1). (PubMed, J Clin Oncol)

Patients with MIBC treated with AMVAC followed by a risk-adapted approach to local consolidation achieved a 2-year MFS rate of 73%. The primary end point was not met, but 17% of all enrolled patients and 48% of the AS group avoided cystectomy without metastatic disease.

6 days ago

P2 data • Journal

RB1 (RB Transcriptional Corepressor 1) • ERCC2 (Excision repair cross-complementation group 2) • FANCC (FA Complementation Group C)

ATM mutation • ERCC2 mutation

cisplatin • doxorubicin hydrochloride • methotrexate • vinblastine

Novel pathogenic ATM mutation with ataxia-telangiectasia in a Chinese family. (PubMed, Front Genet)

This study underscores the importance of genetic testing in A-T diagnosis and provides new insights into the genetic diversity of ATM-related diseases. Further research is needed to understand the broader implications of this mutation.

6 days ago

Journal

ATM (ATM serine/threonine kinase) • AFP (Alpha-fetoprotein)

ATM mutation • AFP elevation

Characterizing Nodal Gamma-Delta T-Cell Lymphoma: Clinicopathological and Molecular Insights. (PubMed, Mod Pathol)

It remains uncertain if nGDTCL represents a distinct entity, and further studies are needed for better characterization. Nonetheless, nodal-based GDTCL should be distinguished from secondary nodal involvement by other extranodal GDTCL and EBV-positive T/NK-cell lymphoproliferative diseases.

7 days ago

Journal • IO biomarker

TP53 (Tumor protein P53) • CD8 (cluster of differentiation 8) • CCR4 (C-C Motif Chemokine Receptor 4) • CD4 (CD4 Molecule) • NCAM1 (Neural cell adhesion molecule 1) • TBX21 (T-Box Transcription Factor 21) • GATA3 (GATA binding protein 3)

TP53 mutation • ATM mutation • CD8 positive • CD4 positive

NCI 9938: M6620 and Irinotecan Hydrochloride in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery (clinicaltrials.gov)

P1, N=66, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Dec 2025

7 days ago

Trial completion date • Combination therapy • Surgery • Metastases

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)

BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation

irinotecan • berzosertib (M6620)

10d

Tumor sequencing before and after neoadjuvant chemoradiotherapy in locally advanced rectal cancer: Genetic tumor characterization and clinical outcome. (PubMed, Clin Transl Radiat Oncol)

Thus, NCRT does not seem to induce a relevant number of new driver mutations or mutational burden. Genetic profiling implies the potential to support tumor-informed approaches and outcome estimation in future.

10 days ago

Clinical data • Journal • Tumor mutational burden • Metastases

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • RYR1 (Ryanodine Receptor 1)

TP53 mutation • KRAS mutation • ATM mutation • RYR1 mutation

11d

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

11 days 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)

13d

Measuring the Effects of Talazoparib in Patients With Advanced Cancer and DNA Repair Variations (clinicaltrials.gov)

P2, N=36, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2026

13 days ago

Trial completion date • Trial primary completion date • Metastases

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1) • 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) • 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)) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCF (FA complementation group F) • FANCL (FA Complementation Group L) • FANCI (FA Complementation Group I) • FANCM (FA Complementation Group M) • BACH1 (BTB Domain And CNC Homolog 1) • 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)

BRCA2 mutation • BRCA1 mutation • ATM mutation

Talzenna (talazoparib)

15d

Efficacy of olaparib combined with dabrafenib and trametinib for a patient with BRAF mutated and ATM deleted metastatic melanoma. (PubMed, J Eur Acad Dermatol Venereol)

No abstract available

15 days ago

Journal • PARP Biomarker • Metastases

BRAF (B-raf proto-oncogene)

BRAF mutation • ATM mutation • ATM deletion

Lynparza (olaparib) • Mekinist (trametinib) • Tafinlar (dabrafenib)

19d

Uterine sarcoma with KAT6B/A::KANSL1 fusion: a molecular and clinicopathological study on 9 cases. (PubMed, Virchows Arch)

Of the 8 patients with available follow-up, two died of disease, 3 are currently alive with disease, and 3 have no evidence of disease. The correct recognition of tumors with the KAT6B/A::KANSL1 fusion is essential because despite the bland morphological features of most cases, these tumors have a propensity for aggressive behavior.

19 days ago

Journal

TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • TSC1 (TSC complex subunit 1) • ERCC3 (ERCC Excision Repair 3, TFIIH Core Complex Helicase Subunit) • FANCD2 (FA Complementation Group D2) • KAT6B (Lysine Acetyltransferase 6B)

TP53 mutation • ATM mutation • PTEN mutation • NF1 mutation • TSC1 mutation • PDGFRB mutation

23d

ATR inhibition potentiates FOLFIRINOX cytotoxic effect in models of pancreatic ductal adenocarcinoma by remodelling the tumour microenvironment. (PubMed, Br J Cancer)

The FOLFIRINOX and VE-822 combination is a promising strategy to improve FOLFIRINOX efficacy and overcome drug resistance in PDAC.

23 days ago

Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • ATR (Ataxia telangiectasia and Rad3-related protein)

ATM mutation

5-fluorouracil • irinotecan • berzosertib (M6620) • leucovorin calcium

25d

The Impact of Genetic Mutations on the Efficacy of Immunotherapies in Lung Cancer. (PubMed, Int J Mol Sci)

This review provides an overview of the mechanisms of FDA-approved immunotherapeutic drugs, offering an updated perspective on the current state and future developments in lung cancer therapy. More importantly, the factors that positively and negatively impact the immunotherapy's efficacy will also be discussed.

25 days ago

Review • Journal • IO biomarker

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • KEAP1 (Kelch Like ECH Associated Protein 1)

TP53 mutation • KRAS mutation • EGFR mutation • BRAF mutation • ATM mutation • NF1 mutation • KEAP1 mutation

25d

Mutations Matter: Unravelling the Genetic Blueprint of Invasive Lobular Carcinoma for Progression Insights and Treatment Strategies. (PubMed, Cancers (Basel))

Current challenges in chemotherapy, along with the targeted therapies, are also discussed. The present article aims to comprehensively review the recent literature, focusing on the pathological and molecular aspects of ILC, including associated genetic mutations influencing disease progression and drug resistance.

25 days ago

Review • Journal • BRCA Biomarker

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • CDH1 (Cadherin 1)

HER-2 negative • ATM mutation

27d

DDRiver Solid Tumours 301: Tuvusertib (M1774) in Participants With Metastatic or Locally Advanced Unresectable Solid Tumors (DDRiver Solid Tumors 301) (clinicaltrials.gov)

P1, N=161, Active, not recruiting, EMD Serono Research & Development Institute, Inc. | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Jan 2025 --> Jan 2026

27 days ago

Trial completion date • Trial primary completion date • Metastases

ARID1A (AT-rich interaction domain 1A) • ATRX (ATRX Chromatin Remodeler)

ATM mutation • ARID1A mutation

Zejula (niraparib) • tuvusertib (M1774)

Investigating the influence of germline ATM variants in chronic lymphocytic leukemia on cancer vulnerability. (PubMed, Haematologica)

In conclusion, we demonstrate a higher prevalence of B-cell lymphoproliferative disorders, including familial CLL, in relatives of CLL patients carrying germline ATM variants. The presence of these germline variants did not impact TTFT compared to patients harboring somatic ATM mutations.

1 month ago

Journal

ATM (ATM serine/threonine kinase)

ATM mutation

Breast cancer and ATM mutations: treatment implications. (PubMed, Hered Cancer Clin Pract)

At present, these women are treated in the same way as women without a mutation. It is important that large prospective studies be conducted looking at various treatment modalities in women with breast cancer and an ATM mutation in order to optimize outcomes.

1 month ago

Review • Journal • BRCA Biomarker

ER (Estrogen receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase)

ER positive • BRCA1 mutation • ATM mutation

2ms

Novel Plasma Cell-Free RNA-Based Liquid Biopsy Approach for CLL (ASH 2024)

Conclusions The presented liquid biopsy-based approach demonstrates the feasibility of identifying malignant cell fraction, BCR repertoires, clinically significant mutations, and immune and tissue specific processes from cfRNA. This study also suggests that the cfRNA platform may support longitudinal monitoring of CLL progression and relapse, as well the development of MRD tests with future validation.

2 months ago

Liquid biopsy • Biopsy

TP53 (Tumor protein P53) • NOTCH1 (Notch 1) • SF3B1 (Splicing Factor 3b Subunit 1) • BIRC3 (Baculoviral IAP repeat containing 3)

TP53 mutation • ATM mutation • SF3B1 mutation • BIRC3 mutation

BostonGene Tumor Portrait™ Test

2ms

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).

2 months 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)

2ms

Genomic Profiles of Early Progressors vs Exceptional Responders on CDK4/6i in ER+ HER2- Advanced Breast Cancer (SABCS 2024)

Pts with HR+ HER2- aBC from a phase II trial of an alternative schedule of palbociclib (palbo alt dosing trial NCT 3007979) and from a retrospective CDK4/6i study were included in this analysis...The majority of these pts received palbo (10/10) paired with letrozole (8/10) and did not have recurrence on adjuvant endocrine therapy (8/10)... Early progression on CDK4/6i is associated with a particularly poor prognosis; however, there are patients with exceptional response to CDK4/6i who may remain on therapy for an extended time. There were variations in the mutation profiles between the two cohorts, though this data set was limited in size. Additional analysis of genomic variants is needed to identify profiles of patients who may significantly benefit from CDK4/6i.

2 months ago

Metastases

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR1 (Fibroblast growth factor receptor 1) • ATM (ATM serine/threonine kinase) • RB1 (RB Transcriptional Corepressor 1) • CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • GNAS (GNAS Complex Locus) • GATA3 (GATA binding protein 3)

TP53 mutation • EGFR mutation • HR positive • HER-2 negative • PIK3CA mutation • ATM mutation • FGFR1 mutation • AR mutation • HR positive + HER-2 negative

Guardant360® CDx

Ibrance (palbociclib) • letrozole

2ms

Clinical Validation of an Ultra-Sensitive ctDNA NGS Assay in HR-Positive, HER2-Negative Breast Cancer Patients (SABCS 2024)

Plasma samples were collected after first-line aromatase inhibitor (AI) therapy and before initiating second-line treatment with Fulvestrant... The PredicineCARE Ultra ctDNA NGS assay showcased a superior ability to detect low tumor fractions and low-frequency mutations in HR-positive, HER2-negative breast cancer patients, significantly outperforming standard liquid biopsy assays. This enhanced sensitivity offers substantial benefits for early identification of treatment resistance and disease progression, potentially allowing for more timely and tailored therapeutic interventions.

2 months ago

Clinical • Next-generation sequencing • BRCA Biomarker • Circulating tumor DNA

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA2 (Breast cancer 2, early onset) • FGFR3 (Fibroblast growth factor receptor 3) • BAIAP2L1 (BAI1 associated protein 2 like 1) • BAIAP2 (BAR/IMD Domain Containing Adaptor Protein 2)

TP53 mutation • HR positive • HER-2 negative • PIK3CA mutation • ATM mutation • FGFR3-BAIAP2L1 fusion

PredicineCARE™

fulvestrant

2ms

Serial circulating tumor DNA (ctDNA) assessment to predict treatment response and identify genomic evolution in patients with metastatic breast cancer (mBC). (SABCS 2024)

Decrease in TF, but not maxVAF, at 1-2 weeks after starting next therapy is correlated with clinical response at time of restaging and can provide an early assessment of treatment response. Genomic evolution with both emerging and disappearing alterations, including in genes clinically actionable in breast cancer as well as genes likely associated with CH, was frequently identified by serial liquid biopsies, both at time of progression and while on treatment.

2 months ago

Clinical • BRCA Biomarker • Circulating tumor DNA • Metastases

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • DNMT3A (DNA methyltransferase 1) • PALB2 (Partner and localizer of BRCA2)

TP53 mutation • PIK3CA mutation • ATM mutation • PTEN mutation • PALB2 mutation

FoundationOne® Liquid CDx

2ms

Integrating ctDNA and Tumor Fraction Features for Deciphering Molecular Response and Resistance Mechanism to Endocrine Therapy and CDK4/6 Inhibition in Advanced HR-positive Metastatic Breast Cancer. (SABCS 2024)

Among those treated with endocrine therapies, 36 were treated with AI combined with Fulvestrant... The sensitive ctDNA NGS assay effectively identified gene variations and tumor fraction levels as prognostic markers in advanced HR-positive breast cancer, demonstrating significant implications for personalized treatment.

2 months ago

Circulating tumor DNA • Metastases

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • FGFR1 (Fibroblast growth factor receptor 1) • RB1 (RB Transcriptional Corepressor 1) • GNAS (GNAS Complex Locus)

TP53 mutation • HR positive • PIK3CA mutation • ATM mutation

PredicineCARE™

fulvestrant

2ms

Clinical Outcomes and the 21-Gene Recurrence Score Assay in Early-Stage Breast Cancer Associated with CHEK2, ATM and PALB2 Germline Pathogenic Variants (SABCS 2024)

Our data demonstrate that higher Oncotype RS, CHEK2 mutations, lymphatic and vascular invasion, and higher Ki67 levels were identified as predictors of poorer RFS. Conversely, older age (>50 years), adjuvant ET, and adjuvant XRT were associated with improved RFS. Importantly, the presence of ATM, CHEK2, or PALB2 mutations did not significantly impact OS.

2 months ago

Clinical • Clinical data

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • ATM (ATM serine/threonine kinase) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2)

ER positive • HR positive • HER-2 negative • ATM mutation • PALB2 mutation • CHEK2 mutation • HR positive + HER-2 negative • PGR negative • HER-2 negative + ER positive

Oncotype DX Breast Recurrence Score®Test

2ms

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

2 months 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

2ms

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.

2 months 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)

2ms

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.

2 months ago

Journal

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

ATM mutation

2ms

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

2 months ago

Trial completion date

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

BRCA1 mutation • HRD • ATM mutation

2ms

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.

2 months 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)

2ms

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.

2 months 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

2ms

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

2 months 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)

2ms

Cohort Study of Pancreatic Cancer Risk (clinicaltrials.gov)

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

2 months 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

2ms

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.

2 months 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

2ms

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.

2 months 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)

2ms

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.

2 months 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

2ms

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.

2 months 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

3ms

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.

3 months 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

3ms

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)).

3 months 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

3ms

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.

3 months ago

Journal

ATM (ATM serine/threonine kinase)

ATM mutation

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

3ms

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.

3 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

3ms

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

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

3 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)

3ms

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.

3 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

3ms

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

3 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