MSH6 (MutS homolog 6)

P=N/A, N=77, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Feb 2026 --> Feb 2027 | Trial primary completion date: Feb 2026 --> Feb 2027

MSI testing which has been used historically to identify patients with Lynch Syndrome and evaluate the severity and prognosis of MSI carcinomas now plays an important role in identifying patients who will benefit from targetable therapy. MMR study therefore recommended in all cases of endometrial carcinomas and detection of MMR proteins by IHC can indirectly reflect the status of MSI and is a reliable method of MSI detection.

P2, N=62, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Feb 2026 --> Feb 2027 | Trial primary completion date: Feb 2026 --> Feb 2027

P2, N=128, Not yet recruiting, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

NGS analysis of the tumor tissue revealed a pathogenic BRCA2 variant (c.1813delA, p.Ile605TyrTer9), which provides a potential target for personalized therapy. This case report highlights the co-segregation of a rare pathogenic MSH2 variant in a Tunisian family and underscores its clinical implications for improving the management and surveillance of patients with Lynch syndrome.

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.

Subsequently, endometrioid adenocarcinoma was diagnosed, and in view of the family history, an underlying genetic disorder was suspected and later confirmed as LS with a pathogenic MSH6 variant, representing only the second reported case of MSH6-associated pituitary adenoma. Surgical management included hysterectomy with bilateral salpingo-oophorectomy, aortopelvic lymphadenectomy, and omental biopsy. This case underscores the importance of early diagnosis and lifelong monitoring in CD to reduce mortality from uncontrolled hypercortisolism, while highlighting a possible association between LS and ACTH-secreting pituitary adenomas, particularly those with MSH6 mutations.

P2, N=0, Withdrawn, M.D. Anderson Cancer Center | N=20 --> 0 | Trial completion date: Sep 2032 --> Jan 2026 | Initiation date: Apr 2026 --> Oct 2025 | Not yet recruiting --> Withdrawn | Trial primary completion date: Sep 2030 --> Jan 2026

P=N/A, N=20000, Recruiting, Arbor Research Collaborative for Health | N=10000 --> 20000

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.

P1/2, N=0, Withdrawn, M.D. Anderson Cancer Center | N=30 --> 0 | Trial completion date: Dec 2032 --> Jan 2026 | Initiation date: Feb 2026 --> Sep 2025 | Not yet recruiting --> Withdrawn | Trial primary completion date: Dec 2030 --> Jan 2026

The supernatant/precipitate of vaginal lavage fluid has significant clinical significance for early screening of endometrial cancer and may also have potential clinical value in guiding targeted therapy and evaluating prognosis. Vaginal lavage fluid gene sequencing may serve as a new method for initial screening of endometrial cancer.