RESUMEN
Familial colorectal cancer type X (FCCTX) is a heterogeneous colorectal cancer predisposition syndrome that, although displays a cancer pattern similar to Lynch syndrome, is mismatch repair proficient and does not exhibit microsatellite instability. Besides, its genetic etiology remains to be elucidated. In this study we performed germline exome sequencing of 39 cancer-affected patients from 34 families at risk for FCCTX. Variant classification followed the American College of Medical Genetics and Genomics (ACMG) guidelines. Pathogenic/likely pathogenic variants were identified in 17.65% of the families. Rare and potentially pathogenic alterations were identified in known hereditary cancer genes (CHEK2), in putative FCCTX candidate genes (OGG1 and FAN1) and in other cancer-related genes such as ATR, ASXL1, PARK2, SLX4 and TREX1. This study provides novel important clues that can contribute to the understanding of FCCTX genetic basis.
Asunto(s)
Quinasa de Punto de Control 2/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , ADN Glicosilasas/genética , Endodesoxirribonucleasas/genética , Exodesoxirribonucleasas/genética , Enzimas Multifuncionales/genética , Adulto , Anciano , Proteínas de la Ataxia Telangiectasia Mutada/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/patología , Reparación de la Incompatibilidad de ADN/genética , Femenino , Predisposición Genética a la Enfermedad , Mutación de Línea Germinal/genética , Humanos , Masculino , Persona de Mediana Edad , Oncogenes/genética , Fosfoproteínas/genética , Recombinasas/genética , Proteínas Represoras/genética , Ubiquitina-Proteína Ligasas/genética , Secuenciación del ExomaRESUMEN
A better understanding of the clinical and molecular features of oropharyngeal squamous cell carcinomas (OPSCC) may help in the development of strategies for a better patient management, improving survival rates. This retrospective study conducted a clinical and molecular characterization of surgically treated OPSCC samples. Paraffin-embedded samples from a series of cases were screened for high-risk (HR) human papillomavirus (HPV) infection, methylation of a 5-gene panel, p53 expression, and TP53 mutation. The study was conducted at Barretos Cancer Hospital. Twenty-five surgically treated OPSCC with available tissue were included in the study. Samples were classified according to HPV status and molecular features and some of these characteristics were associated to clinical data. Twenty percent of the cases were HR-HPV positive and 62.5% presented TP53 mutations. DAPK hypermethylation was associated with HPV status (p = 0.023), while methylated CCNA1 was inversely related to TP53 mutations in primary tumors (p = 0.042) and associated with a better disease-free survival (22.3% vs. 100.0%; p = 0.028) and overall survival (8.0% vs. 100.0%; p = 0.012). The results show differences regarding molecular and clinical characteristics in the oropharynx cases identified that should be validated in more cases to confirm whether these differences are able to classify patients according to outcome and help in a more thorough patient management.