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Exp Mol Med. 2018 Feb 9;50(2):e442. doi: 10.1038/emm.2017.265.

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

Han MR1,2, Shin S1,2,3, Park HC1,2, Kim MS4,5, Lee SH6, Jung SH1,2,5, Song SY7, Lee SH4,5, Chung YJ1,2,3.

Author information

1
Department of Integrated Research Center for Genome Polymorphism, The Catholic University of Korea, Seoul, Korea.
2
Precision Medicine Research Center, The Catholic University of Korea, Seoul, Korea.
3
Department of Microbiology, The Catholic University of Korea, Seoul, Korea.
4
Department of Pathology, The Catholic University of Korea, Seoul, Korea.
5
Cancer Evolution Research Center, The Catholic University of Korea, Seoul, Korea.
6
Department of Hospital Pathology, The Catholic University of Korea, Seoul, Korea.
7
Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

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.

PMID:
29422544
PMCID:
PMC5903820
DOI:
10.1038/emm.2017.265
[Indexed for MEDLINE]
Free PMC Article

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