MLH1 (MutL homolog 1)

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.

As cytoplasmic localization occurs in ~11% of ER+ patients, it represents a contributor to MLH1 dysregulation. Incorporating cytoplasmic MLH1 localization into diagnostics could guide the use of CDK4/6 inhibitors in this hard-to-treat subset.

In conclusion, discordance between IHC- and NGS-based MMR/MSI detection is primarily attributable to MSH6 loss with MSH3 compensation and MLH1 promoter methylation. Recognizing these mechanisms is essential for accurate molecular subtyping and clinical decision-making in EC.

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.

This case underscores the importance of comprehensive assessment integrating tumor and germline molecular data, particularly when clinical or molecular findings are atypical or discordant. The digenic etiology also raises questions regarding cancer surveillance and management strategies in such individuals.

Comprehensive molecular profiling can help guide personalized immunotherapy decisions. Further studies are needed to confirm long-term benefits, optimize treatment duration and dosing, and identify predictive biomarkers for high-risk CRC.

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.

This study underscores the importance of assessing and mitigating unintended epigenetic consequences in genome editing applications, as such changes can profoundly affect gene regulation and cellular function.

Results demonstrated that these phytochemicals exhibited superior binding affinities compared to standard therapy, 5-fluorouracil, with alpha-tocopherol notably outperforming it...Stability assessments showed consistent parameters throughout the simulation. Overall, the prioritized phytochemicals from A. muricata, especially alpha-tocopherol, exhibit significant anticancer potential and stability, supporting further experimental validation and development as therapeutic agents for colon cancer.

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

These data highlight the importance of dMMR testing in patients with advanced solid tumors in China to optimize biomarker testing and treatment decisions.

MSS/EMAST-L tumors aligned with chromosomally stable, KRAS/Wnt-driven CRC. In conclusion, MSS/EMAST-H tumors represent an underrecognized CRC subtype with intermediate genomic instability and a distinctive molecular profile, with potential implications for prognostic assessment and personalized therapeutic strategies.