MUTYH (MutY homolog)

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.

Compared with the conventional marker AFP, MUTYH demonstrates superior diagnostic and prognostic evaluation efficacy and is associated with anti-PD-1/PD-L1 therapeutic response and sorafenib resistance. Overall, MUTYH has potential as a novel biomarker and therapeutic target for HCC.

Given that the MUTYH mutation is rarely seen in cases of colorectal cancers, we believe that our findings may contribute to identifying potential clinical and therapeutic implications for individuals with this mutation.

Post hoc analyses suggested sufficient statistical sensitivity to detect the observed differences; however, results should be interpreted considering the retrospective, single-center design. These findings support the clinical value of incorporating non-BRCA genes into multigene testing strategies in Argentina and underscore the need for larger multi-center studies to confirm these observations and refine genetic counseling and surveillance strategies in Latin American populations.

A minimally invasive subtotal colectomy was proposed to a 41-year-old man whose genetic testing for polyposis and hereditary cancer syndromes revealed a rare homozygotic variation of uncertain significance (VUS)+ in the MUTYH gene. Absence of rectal involvement made rectal sparing possible in association with close endoscopic follow-up.

Among overall identified PVs, six were novel: APC c.3405T > G, APC c.419_422delAGAG, PMS1 c.1258delC, MLH1 c.1291_1292delAT, NBN c.877delA, and EPCAM c.184 + 1G > A. The observed prevalence of clinically actionable PVs in both patients and their relatives highlights the potential clinical value of multigene panel testing and cascade screening strategies in Kazakhstan.

Subsequent next-generation sequencing of the lymph node metastasis revealed a novel heterozygous MUTYH frameshift mutation, c.848delT (p.M283Rfs*3), which was confirmed to be of germline origin by Sanger sequencing of the patient's normal thyroid tissue. This case expands the disease spectrum associated with heterozygous MUTYH carriers and enhances the understanding of the phenotypic heterogeneity of tumors in this population.

Furthermore, patients with MEN1 P/LPVs had more mediastinal tumors and a younger age than those with non-MEN1 P/LPVs. This study, which is the largest to date regarding germline variations in Chinese patients with NETs, reveals a distinct mutational profile and identifies the unique clinicopathological features among carriers of germline P/LPVs.

Genetics has been shown to affect several aspects of disease, including carcinogenesis, onset age, clinicopathological features, prognosis, and therapy response. In this review, we will investigate the impact of germline PVs in different genes on genetic susceptibility to the development of inherited EC, discussing the potential cancer risk in mutation carriers as well as prognostic implications and current therapeutic approaches, also evaluating the possibility of carrying out a more extensive routine genetic analysis for EC women, in order to increase the diagnostic power, improve prevention and surveillance strategies in genetically predisposed subjects, and implement tailored therapies.