Multiple alterations on genes encoding components of the SWItch/Sucrose Non-Fermentable complex could be found in human papillomavirus-negative cervical cancer.

Abstract

Cervical cancer without apparent association with human papillomavirus (HPV) infection is a rare type of the malignancy with poor prognosis but little is known about it. With HPV vaccine becoming widely accepted, it is expected that the proportion of HPV-negative cancer will rise. Understanding the molecular etiology of HPVnegative cancer is therefore important for the management of cervical cancer in the future. To compare the genetics of HPV-negative and -positive tumors, we characterized the coding genomes of 24 cervical cancers with known high-risk HPV (hrHPV) statues verified by INNO-LiPA HPV Genotyping Extra II assay using whole-exome sequencing (WES). In total we analyzed 4 HPV-negative and 20 HPV-positive cervical cancer samples by WES. There was no significant difference between the number of nonsynonymous SNPs and INDELs between HPV-negative and HPV-positive cancers. Here a preliminary analysis of the WES data focusing on 27 genes encoding components of the (SWItch/Sucrose Non-Fermentable) SWI/SNF complex is presented. In contrast to previous genomic data form TCGA, no protein changing SNP or INDEL was identified on ARID1A. Instead a small insertion adding one amino acid to the ARID1B protein was found in one of the HPV-negative cancers but not in the HPV-positive cases. Several SNPs were also found on some other genes encoding subunits of SWI/SNF complex in at least one of the HPV-negative cancers. Our data suggested that while mutations in SWI/ SNF complex are common among HPV-negative cervical cancers, the genetic makeup of HPV-negative cervical cancer may be more diversified than previously identified.