News - ATM biallelic inactivation

over1year

Associations Between Cancer Predisposition Mutations and Clonal Hematopoiesis in Patients With Solid Tumors. (PubMed, JCO Precis Oncol)

Our results suggest a close relationship between inherited variants and CH mutations within the DDR genes in patients with solid tumors. Associations identified in this study might translate into enhanced clinical surveillance for CH and associated comorbidities in patients with cancer harboring these germline mutations.

over 1 year ago

Journal

TP53 (Tumor protein P53) • ATM (ATM serine/threonine kinase) • CHEK2 (Checkpoint kinase 2) • PPM1D (Protein Phosphatase Mg2+/Mn2+ Dependent 1D)

TP53 mutation • ATM mutation • CHEK2 mutation • PPM1D mutation • ATM biallelic inactivation

MSK-IMPACT

over2years

Germline Pathogenic Variants Impact Clinicopathology of Advanced Lung Cancer. (PubMed, Cancer Epidemiol Biomarkers Prev)

The family members of lung cancer patients harboring PV in cancer predisposing genes should be referred for genetic counseling and may benefit from proactive surveillance.

over 2 years ago

Journal • BRCA Biomarker

EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • BAP1 (BRCA1 Associated Protein 1) • CHEK2 (Checkpoint kinase 2)

ATM biallelic inactivation

over3years

Dissecting the role of TP53 alterations in del(11q) chronic lymphocytic leukemia. (PubMed, Clin Transl Med)

Our work highlights that combined monoallelic del(11q) and TP53 alterations coordinately contribute to clonal advantage and shorter overall survival in CLL.

over 3 years ago

Journal

TP53 (Tumor protein P53) • ATM (ATM serine/threonine kinase)

TP53 mutation • ATM mutation • Chr del(11q) • TP53 mutation + Chr del(17p) • ATM biallelic inactivation

4years

CRISPR/Cas9-generated models uncover therapeutic vulnerabilities of del(11q) CLL cells to dual BCR and PARP inhibition. (PubMed, Leukemia)

Ex vivo studies in the presence of stromal stimulation on 38 CLL primary samples confirmed a synergistic action of the combination of olaparib and ibrutinib in del(11q)/ATM-mutated CLL patients. In addition, we showed that ibrutinib produced a homologous recombination repair impairment through RAD51 dysregulation, finding a synergistic link of both drugs in the DNA damage repair pathway. Our data provide a preclinical rationale for the use of this combination in CLL patients with this high-risk cytogenetic abnormality.

4 years ago

Journal • PARP Biomarker

ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • RAD51 (RAD51 Homolog A)

ATM mutation • Chr del(11q) • ATM biallelic inactivation

Lynparza (olaparib) • Imbruvica (ibrutinib)