ATM mutation

T297 is located in the middle domain of HSP90, a region that is involved in the interaction of HSP90 with clients. Consistently, structural studies indicate that T297 phosphorylation can indeed favor the chaperone's interaction with HER2, further supporting our hypothesis.

Our results suggest expansion of the phenotypic spectrum of some of these DDRG to include MM. The identification of these germline predisposition genes opens the avenue for targeted screening of higher risk individuals especially those with young-onset or a family history of plasma cell gammopathies.

Following a diagnosis of metastatic PDAC, the patient achieved complete remission after retreatment with FOLFIRINOX and has maintained remission for over 40 months on olaparib maintenance therapy...Our findings advocate for further clinical studies to assess the broader applicability of PARP inhibitors in PDAC patients with HRD mutations, including ATM and BRIP1, which could enhance survival outcomes in this high-risk population. Expanding the standard of care to include PARP inhibitors for HRD-positive PDAC could address a critical gap in treatment and improve patient prognosis.

BM eosinophilia or basophilia was not uncommon. MDS with BM eosinophilia exhibited distinct mutational profiles including DDR genes mutations, which may attribute to adverse clinical outcomes. Identification of these subtypes can aid in prognosis and potentially guide targeted therapeutic approaches.

Clinical-radiomics ML models based on PSMA PET imaging show promising accuracy in predicting actionable genomic alterations in mPCa. These findings support further investigation into radiogenomics modelling as a complementary, non-invasive tool to inform molecular profiling and treatment stratification.

The majority of CDK12-mutated tumors exhibited a distinct type of copy number variations (CNV)-a tandem duplication phenotype. Our study suggests that the selection of PC patients for PARPi treatment requires a significant revision of existing attitudes towards tumor genetic profiling.

This case emphasizes the importance of considering A-T in children with recurrent chest infections and neurological symptoms. Early diagnosis facilitates timely supportive care, including immunization, pulmonary management, malignancy surveillance, and genetic counseling for families.

The totality of current evidence suggests that germline DDR pathway mutations not only predispose to well-established solid malignancy syndromes but also to CH, which independently increases the risk of hematologic malignancies. Recognizing germline contributions to CH has broad implications for risk assessment, surveillance strategies, and development of preventive strategies in myeloid neoplasia.

This series underscores the sensitivity of ATM-mutated mCRC to DNA-damaging chemotherapy and highlights the potential role of PARPi. The therapeutic benefit of PARPi in these patients cannot be fully separated from concurrent chemotherapy, and the observed responses are likely to reflect combined effects. Nonetheless, these findings suggest potential synergy and warrant further investigation of PARP inhibition, alone or in combination, in biomarker-selected mCRC population.

These results identified GRP94 as an ATM interactor and apparent substrate and demonstrated specific critical regulatory roles for ATM outside of DNA damage signaling. These insights provide potential explanations for several of the phenotypes associated with ATM dysfunction and potential opportunities for novel approaches to blunt clinical symptoms in A-T, and also suggest that other neurodegenerative and inflammatory disorders might benefit from selective inhibition of cell surface GRP94.

We identified 9 significantly mutated genes, some of which are known drug targets. Among individual genes, only the BRAF p.V600E mutation was significantly associated with DS-survival, suggesting a limited survival impact from mutations driving colorectal cancer development.

P1/2, N=49, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting | N=84 --> 49