MUTYH (MutY homolog)

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.

PNST harboring oncogenic ERBB2 mutations are multifocal, spanning various neurofibroma variants, including plexiform type, in the absence of clinical or germline evidence of syndromic disease. Our findings suggest ERBB2 mutations may represent an alternative mechanism driving neurofibroma genesis, with potential therapeutic implications.

This work underscores the value of independent functional assays for accurately assessing variant dysfunction and classification. Analysis of MUTYH variants highlights the complexity of the roles of MUTYH in preserving genomic integrity.

Conclusions Lenvatinib showed substantial efficacy in BRAF-mutated PTC, while TERT mutations did not predict poor outcomes. The identification of five genes associated with early treatment failure highlights the potential for genomic biomarkers to guide personalized therapy.

P=N/A, N=1500, Active, not recruiting, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Three pathogenic variants, BRCA2 [c.6509A>G; c.7879A>T; c.5574_5577delAATT] and PALB2 [c.1592delT], were identified in high-risk genes important for breast cancer prediction. Identification of population-based variants may improve breast cancer screening and management in Sri Lanka.

The highly prevalent FLT3 T227M (rs1933437) variant was predicted to alter receptor dimerization and potentially modulate sunitinib binding...These findings demonstrate how pharmacogenomics-guided structural analysis can reveal mechanistic links between OSCC-associated variants and therapeutic response. While our results are based on in silico modeling, they provide a biologically grounded framework for prioritizing variants for experimental validation and for advancing population-specific precision oncology in OSCC.

In the absence of regulation, inappropriate and imbalanced DG activity may trigger telomeric instability, changes in transcriptional profiles and cell death. This review focuses on summarizing key features of OGG1 and MUTYH function, with a special emphasis on structure, regulation, and novel emerging roles.

Non-BRCA1/2 genes, particularly CHEK2 and ATM, substantially contribute to the spectrum of pathogenic variants detected in hereditary cancer testing. The identification of numerous pathogenic and novel variantssupports the clinical utility of broad multigene panel testing, while highlighting the need for careful interpretation of VUS in clinical practice.

The patient was treated with neoadjuvant chemotherapy followed by unilateral mastectomy. This case illustrates the clinical utility of evaluating all foci in multifocal high-grade disease to ensure appropriate systemic therapy and highlights the challenges of interpreting germline variants in the absence of well-described genotype-phenotype associations.

Integrating germline testing into surveillance redefines the management of familial PC. It uncovers hereditary susceptibility beyond classical criteria and supports cascade testing. PC also arises in mutation-negative HRI. #NCT05724992.

In non-hereditary colorectal cancer survivors, overall SPC risks are not elevated, but early-onset cases have higher risks and therefore warrant targeted surveillance and follow-up. National Institutes of Health (U01 CA167551) and National Health and Medical Research Council (1194392).