MUTYH (MutY homolog)

While phenotypes often align with the most penetrant allele, spesific instances may hint at the potential for synergistic effects in certain individuals. Management should transition toward personalized, multi-variant surveillance strategies incorporating both SNV and CNV data.

Our findings suggest that germline testing may play a role in the standard-of-care management of pNEN. MUTYH alterations merit further evaluation as a potential risk factor for pNEN.

Universal germline testing in unselected NEN patients identified clinically relevant PGVs in over 15% of cases. These findings support broader genetic testing approaches to guide treatment, enhance familial risk assessment, and inform cascade testing-regardless of traditional clinical selection criteria.

Germline P/LP mutations were identified in 15.7% of Korean children and AYAs with CNS tumors, most commonly in gliomas and other CNS tumors. Our findings highlight the molecular heterogeneity of germline predisposition in CNS tumors and emphasize the importance of germline testing for risk assessment and surveillance.

Most individuals receiving medically actionable results through DTC-GT had no prior knowledge of their genetic health risks, despite many reporting a relevant personal and/or family history. When individuals shared results with HCPs and received medical recommendations, adherence was high.

This study reveals distinct germline mutation patterns and clinical features in Chinese CRC patients, underscoring the need for population-specific genetic testing and tailored screening to improve prevention, early detection, and personalized treatment in Asian populations.

AMF interacts with MSTN, inhibiting its downstream signaling, promoting myogenic differentiation, and alleviating muscle atrophy, highlighting its potential as a natural therapeutic for muscle-wasting conditions. Through computational modeling, MD simulations, and experimental validation, AMF demonstrates strong binding to MSTN, with confirmed efficacy in both in vitro and in vivo studies.

Among the three-suspected MAP cases with VUS, two harbored somatic KRAS-G12C and/or PIK3CA-Q546K, providing sufficient evidence to reclassify MUTYH VUS p.Pro301Arg and p.Trp113Arg as likely pathogenic based on ACMG/AMP criteria. These findings support the use of KRAS-G12C and PIK3CA-Q546K as cost-effective, accessible tumor biomarkers for aiding in MAP diagnosis and MUTYH VUS reclassification, particularly in settings with limited access to whole-exome/genome mutational signature analysis.

This study demonstrates poor facility-level adherence with MSI/MMR testing recommendations and poor patient-level compliance with genetic referrals in rectal cancer. When recommendations were met, patients with germline mutations benefited from adjustments to their disease management.

In the HAIC cohort, several DDR genes, including ATR, BRCA2, CDK7, MUS81, MUTYH, PARG, POLH, POLK and XPA, were significantly lower in the objective response group. DDR components represent candidate biomarkers and therapeutic targets whose inhibition may enhance oxaliplatin efficacy in HCC.

Mutational signatures in cancers can result in part from non-rare germline variation in DNA repair. The specific effect of MUTYH heterozygosity on CRC risk plausibly reflects the high baseline levels of oxidative damage and SBS18 activity in the colorectum.

In this large Japanese real-world cohort, genomic associations with nivolumab outcomes differed by tumor site. In gastric cancer, ASXL1 mutation was associated with prolonged treatment benefit under PD-1 blockade, while CDH1 and FANCG showed exploratory associations with OS. These findings warrant further validation in prospective and platform-controlled analyses.