Prognostic implications of a molecular classifier derived from whole ‐exome sequencing in nasopharyngeal carcinoma

We proposed three prominent NPC genetic subtypes: RAS/PI3K/AKT, cell ‐cycle, and unclassified using the whole‐exome sequencing. Survival analysis indicated that there were statistically significant among patients with three subgroups. This result reflects the genetic alterations of NPC with distinct mutations and/or copy number changes and provides a roadmap for developing new prognostic biomarkers and targeted therapies. AbstractThe aim of this study was to use whole ‐exome sequencing to derive a molecular classifier for nasopharyngeal carcinoma (NPC) and evaluate its clinical performance. We performed whole‐exome sequencing on 82 primary NPC tumors from Sun Yat‐sen University Cancer Center (Guangzhou cohort) to obtain somatic single‐nucleotide variants, indels, and copy number variants. A novel molecular classifier was then developed and validated in another NPC cohort (Hong Kong cohort, n = 99). Survival analysis was estimated by the Kaplan‐Meier method and compared using the log‐rank test. Cox proportional hazards model was adopted for uni variate and multivariate analyses. We identified three prominent NPC genetic subtypes: RAS/PI3K/AKT (based onRAS,AKT1, andPIK3CA mutations), cell ‐cycle (based onCDKN2A/CDKN2B deletions, andCDKN1B andCCND1 amplifications), and unclassified (based on dominant mutations in epigenetic regulators, such asKMT2C/2D, or the Notch signaling pathway, such asNOTCH1/2). These subtypes differed in survival analysis, with good, i...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research