CHEK2 mutation

P1, N=18, Recruiting, Pamela Munster | Trial completion date: Feb 2027 --> Jan 2028 | Trial primary completion date: Jan 2026 --> Jan 2028

Constitutional CHEK2 mutations combined with somatic NF1 defect may have promoted the malignant progression of SEGA-imitating fibrous meningioma and its favorable initial response to mTOR inhibitors.

Germline mutations in the APC gene were confirmed in more than 90% of Hungarian patients with clinically suspected FAP. Although the role of VUS genes is unclear, they are highly likely to play a role in the development of CRC.

The integration of additional biomarker assessments into MTB workflows enhances precision oncology by expanding the pool of patients eligible for targeted therapies.

Chek2-deficient HSPCs persist in vivo following chemotherapy exposure and exhibit elevated levels of DNA damage compared to wild-type cells. Our findings establish that CHEK2 loss promotes chemoresistance in HSPCs, offering new insights into the role of CHEK2 in therapy-related clonal hematopoiesis observed in cancer patients.

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.

This is the first MINAS-focused analysis from a Turkish cohort. Although uncommon, MINAS represents a significant subset of genetically high-risk individuals requiring tailored clinical management.

This case highlights that the histopathologic features of BAP-1-inactivated melanocytoma can be seen in the setting of an underlying germline mutation other than BAP-1 inactivation. Further study of melanocytic tumors showing BIMT-like histology but with normal BAP1 immunostaining is warranted, because some may contain clues to underlying germline mutations related to family cancer predisposition.

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.

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.

Expert pathology review at a tertiary cancer centre, using comprehensive immunohistochemistry-including paired box gene 8 (PAX8), cancer antigen 125 (CA-125) and hepatocyte nuclear factor 1 beta (HNF1Beta) positivity alongside negative prostatic markers-established a final diagnosis of metastatic clear cell seminal vesicle adenocarcinoma invading the prostate. Despite therapies targeting a checkpoint kinase 2 (CHEK2) mutation (a poly(ADP-ribose) polymerase (PARP inhibitor)), followed by taxanes, platinum-based chemotherapy and radiosurgery for brain metastases, he ultimately succumbed to a stroke linked to his malignancy.

These findings highlight the need to molecularly characterize these lesions as there is no specific histologic finding to identify cases that harbour different pathogenic alterations in specific genes.