Prevalent somatic BRCA1 mutations shape clinically relevant genomic patterns of nasopharyngeal carcinoma in Southeast Europe.

摘要: Genomic patterns of nasopharyngeal carcinomas (NPC) have as yet been studied in Southeast Asian (SEA) patients. Here, we investigated genomic locally advanced NPC European (SEE) patients treated with chemo-radiotherapy. We examined 126 tumors (89% EBV positive) from Greek and Romanian massively parallel sequencing. Paired tumor-cell-rich (TC) infiltrating-lymphocyte-rich (TILs) samples were available 19, paired tumor – germline 68 cases. Top mutated genes BRCA1 (54% all tumors); BRCA2 (29%); TP53 (22%); KRAS (18%). Based on the presence number mutations genes, classified stable (no mutations, n=27); unstable (>7 multiple positive, n=21); intermediate stability (1-7 singly n=78). p.Q563* was present 59 (48%), more frequently (p<0.001). No pathogenic identified. exhibited APOBEC3A/B nucleotide-excision-repair-related mutational signatures. As compared to TC, TILs demonstrated few shared a higher low frequency private In multivariate analysis models for progression-free survival, positivity favorable prognosticator tumors; unfavorable only stability. conclusion, other than described SEA NPC, somatic common SEE NPC; these between TC TILs, appeared affect patient outcome according status. Along identified signatures, novel data may be helpful designing new treatments NPC. This article is protected by copyright. All rights reserved.