Exp Mol Med.  2018 Feb;50(2):e442. 10.1038/emm.2017.265.

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

Affiliations
  • 1Department of Integrated Research Center for Genome Polymorphism, The Catholic University of Korea, Seoul, Korea. yejun@catholic.ac.kr
  • 2Precision Medicine Research Center, The Catholic University of Korea, Seoul, Korea.
  • 3Department of Microbiology, The Catholic University of Korea, Seoul, Korea.
  • 4Department of Pathology, The Catholic University of Korea, Seoul, Korea. suhulee@catholic.ac.kr
  • 5Cancer Evolution Research Center, The Catholic University of Korea, Seoul, Korea.
  • 6Department of Hospital Pathology, The Catholic University of Korea, Seoul, Korea.
  • 7Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. yodasong@hanmail.net

Abstract

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.


MeSH Terms

Carcinoma, Squamous Cell*
Epithelial Cells*
Papillomaviridae
Vulva*
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