MSH2 (MutS Homolog 2)

MDR analysis predicted the best interaction model (MSH2 118 T > C, IVS 1 + 9 G > C, T > C/-6) with a maximum CVC of 10/10 and the least prediction error of 0.355, accompanied by a significant p-value. Furthermore, MD simulations reveal that the Gly322Asp polymorphism in MSH2 induces pronounced structural destabilisation, which may compromise DNA binding and repair efficiency.

In our cohort, the addition of MLPA provided an incremental yield of seven pathogenic CNVs, representing an 11.6% absolute increase in diagnostic sensitivity (from 16.7% to 28.3%) over the NGS-alone workflow, with CNVs accounting for 41% of all pathogenic findings. Our results show that MLPA is a very useful method in molecular diagnostics of LS and its implementation in routine genetic testing in combination with NGS using multigene panel testing would benefit both patients and health care providers.

Segmental and total colectomy offer similar survival and quality-adjusted life year outcomes. With decreased risk of metachronous cancers, patients with MSH6 mutations across all ages may prefer segmental resection due to higher quality-adjusted life years and lower survival benefits from total colectomy compared with MLH1 and MSH2 patients. Operative strategy in patients with hereditary nonpolyposis colorectal cancer should be individualized, and this study shows that mutation-specific differences in survival and quality-adjusted life years are small. See Video Abstract.

While not significantly associated with tumor grade or patient demographics, MMRD may have clinical relevance in specific subgroups. NGS findings highlight the potential utility of integrating molecular diagnostics for identifying MSI and guiding immunotherapy decisions.

P=N/A, N=310, Recruiting, Washington University School of Medicine | Trial completion date: Jan 2028 --> Jan 2027 | Trial primary completion date: Jan 2028 --> Jan 2027

Cascade testing achieved remarkable uptake, with >20 relatives tested in family A-over tenfold higher than typical reports-facilitated by direct clinician contact and streamlined logistics such as convenient blood collection. This is the first documented EPCAM-MSH2 deletion reported from the Middle East and North Africa region (MENA).

IHC testing can discriminate between sporadic and MTS-associated sebaceous neoplasms, but diagnostic utility is limited by low specificity. Most MMR-deficient cases are not due to MTS.

Using cell models we demonstrate IL-6-induced binding of wild type and Δ27bpMSH3 to the NFκB activating complex NEMO/IKKγ which stabilizes MSH3 after disengaging from its nuclear partner MSH2, linking inflammation with DNA repair protein stability. Additional NLS modifications using MSH3-FLAG mimics cytosolic Δ27bpMSH3 retention to cause loss-of-function after inflammation.

The possibility of incorporating these indicators into risk stratification models for precision medicine and early cancer surveillance is highlighted. For this high-risk group, bridging the domains of andrology and oncology may allow for better counseling, earlier detection, and focused therapies.

Therapeutic annotation using OncoKB identified 223 actionable or likely oncogenic variants, highlighting potential targets for precision oncology. This study provides a comprehensive characterization of the breast cancer mutational landscape in MENA patients and offers a valuable resource for advancing genomic and therapeutic research in this demographic.

No associations were found between hMSH2 and hMSH6 expression and tumor staging, HER2, ER, PR, or Ki-67 expression. Our results suggest that the expression of the proposed markers is decreased in breast tumorigenesis.

Specifically, we observed that MSH2 and MSH6 - core components of mismatch repair - are associated with elevated RS and may indicate a shift toward NHEJ-mediated repair under stress conditions. Our study provides a refined approach to quantify RS and sheds light on its broader impact on DNA repair network dynamics.