Integrated Genomic Analysis Suggests MLL3 is a Novel Candidate Susceptibility Gene for Familial Nasopharyngeal Carcinoma

摘要: Background: Little is known about genetic factors associated with nasopharyngeal carcinoma (NPC). To gain insight into NPC etiology, we performed whole exome sequencing on germline and tumor DNA from three closely related family members NPC. Methods: The was ascertained through the Pediatric Familial Cancer Clinic at University of Chicago. diagnosis confirmed pathologically for each individual. For sample sequenced, 97.3% covered 5x, an average depth 44x. Candidate somatic variants were identified prioritized using a custom pipeline. Results: We discovered 72 rare deleterious in 56 genes shared by all individuals. Of these, only are previously NPC-associated genes, which located within MLL3, gene to be somatically altered One variant introduces early stop codon predicts complete loss-of-function. Tumor analysis revealed mutations EBV integration events; none, however, among Conclusions: These data suggest that inherited MLL3 may have predisposed these individuals single develop NPC, cooperate individually-acquired or events etiology. Impact: Our finding first instance plausible candidate high penetrance mutation predisposing