Mutational signatures and chromosome alteration profiles of squamous cell carcinomas of the vulva

摘要

Vulvar squamous cell carcinoma (SCC) consists of two different etiologic categories: human papilloma virus (HPV)-associated (HPV (+)) and HPV-non-associated (HPV (?)). There have been no genome-wide studies on the genetic alterations of vulvar SCCs or on the differences between HPV (+) and HPV (?) vulvar SCCs. In this study, we performed whole-exome sequencing and copy number profiling of 6 HPV (+) and 9 HPV (?) vulvar SCCs and found known mutations ( TP53 , CDKN2A and HRAS ) and copy number alterations (CNAs) (7p and 8q gains and 2q loss) in HPV (?) SCCs. In HPV (+), we found novel mutations in PIK3CA , BRCA2 and FBXW7 that had not been reported in vulvar SCCs. HPV (?) SCCs exhibited more mutational loads (numbers of nonsilent mutations and driver mutations) than HPV (+) SCCs, but the CNA loads and mutation signatures between HPV (+) and HPV (?) SCCs did not differ. Of note, 40% and 40% of the 15 vulvar SCCs harbored PIK3CA and FAT1 alterations, respectively. In addition, we found that the SCCs harbored kataegis (a localized hypermutation) in 2 HPV (+) SCCs and copy-neutral losses of heterozygosity in 4 (one HPV (+) and 3 HPV (?)) SCCs. Our data indicate that HPV (+) and HPV (?) vulvar SCCs may have different mutation and CNA profiles but that there are genomic features common to SCCs. Our data provide useful information for both HPV (+) and HPV (?) vulvar SCCs and may aid in the development of clinical treatment strategies.