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

This is the authors' abstract. We don't add key points for this paper.

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. Genetic analysis has revealed mutations and chromosome alterations in skin cancers known as squamous cell carcinomas affecting the vulva. There are two types of squamous cell carcinoma (SCC) of the vulva. The HPV(+) type is associated with human papilloma virus infection, unlike the HPV(-) type. Mi-Ryung Han and colleagues at The Catholic University of Korea in Seoul investigated cells from patients with each type of the disease. In cells of the HPV(-) cancer they found some previously known types of mutation, together with specific repeated sections of chromosomes. In HPV(+) cells they identified three mutations not previously found in vulvar SCCs. These and other distinguishing genetic features should help to understand vulvar skin cancer and may also prove useful for devising new treatments.