PMS2 (PMS1 protein homolog 2)

This case highlights that lung adenocarcinoma can be a manifestation of LS and underscores the critical importance of retrospective MMR testing in establishing the diagnosis. Furthermore, it demonstrates the efficacy of immune checkpoint inhibitions in advanced dMMR tumors.

An exploratory approach consisting of unmasking the results of the NGS analysis of 123 « research » genes involved in the carcinogenesis was applied to the 447 patients tested negative for the different genes of our diagnostic panel. This approach failed to identify other susceptibility genes to pancreatic adenocarcinoma.

This copula-based meta-analysis identifies gene-specific risks of endometrial and ovarian cancer in female Lynch syndrome carriers, supporting personalized gynecologic surveillance. It also notes higher breast cancer risks in MSH6 and PMS2 carriers, but conflicting evidence from large perspective databases prevents definitive conclusions about breast cancer as part of the Lynch syndrome spectrum.

Although dMMR was associated with initial treatment resistance, its unique immunogenicity was found to influence disease progression and subsequent treatment options. These findings suggested that MMR testing in LA-HNSCC patients had significant clinical value, not only aiding in the identification of patients who might benefit from subsequent immunotherapy but also potentially informing initial treatment strategies, such as the prospective exploration of combined immunotherapy approaches.

This study is limited due to a small cohort and limited available clinical data. Larger cohort studies and prospective clinical trials are necessary to validate and explore the interplay between molecular and immune biomarkers as well as general biological mechanism in paving therapeutic way in melanoma.

MLH1 loss identifies a subset of MMRd ECs with worse outcomes and lower CD8+ densities supporting substratification of this molecular subtype. Grade, histotype, ER, PR, L1CAM, CTNNB1 and p53 status do not add prognostic refinement within MMRd EC.

Genomic classifier tools help identifying aggressiveness of cancers and aid in personalized treatment decision-making. Joint efforts of multidisciplinary physicians are crucial to improve health outcomes for patients with PCa across the spectrum of this disease.

These findings suggest that current surveillance recommendations for individuals with LS should be re-evaluated. Lynch-Polyposis.

We present a series of five children who developed cancer prior to the age of 20 years (range: 2-12 years) with malignancies including colonic adenocarcinoma (N = 1), T-lymphoblastic lymphoma (N = 3), and high-grade glioma (N = 4). Two patients with MSH6 alterations developed a constellation of three primary tumors: high-grade glioma, T-lymphoblastic lymphoma, and colonic neoplasia including colonic adenocarcinoma in one patient and a tubular adenoma in the other.

This study shows no single case with MSI in the NSND subgroup of HNSCC. Although a deficient DNA mismatch repair system is a predictive biomarker for response to immune checkpoint inhibitors, we found no evidence to support routine analysis of MSI in HNSCC, also not in the subgroup of NSND.

MMR protein expression in HNSCC varies by HPV status and demographic factors and is linked to differential immune infiltration. These findings suggest that MMR protein imbalance may influence tumor immunogenicity and could potentially serve as a biomarker to inform therapeutic strategies in the immunotherapy era, especially in p16-negative tumors.

In 11% of patients, the identified CPG GVs potentially sensitized to targeted therapies, such as PARP, immune checkpoint, or EGFR inhibitors. In conclusion, our study identifies CPGs and novel genes relevant in germline testing of glioma patients with a familial/personal tumor history, possibly resulting in targeted treatment options.