ARID1A in cervical cancer

Abstract

Background: Persistent HPV infection has been established as a necessary factor for cervical carcinogenesis. However, evidence supporting the existence of HPV-negative cervical cancer is emerging. A recent comprehensive genomic-wide characterization of cervical cancers indicated that HPV-negative cervical cancers are likely to harbor loss-of-function mutations in the gene encoding a SWI/SNF complex component AT-rich interactive domain-containing protein 1A (ARID1A). Objective: The aim of this study was to determine the mutation status and protein expression of ARID1A in HPV-negative cervical cancer. Methods: Exons 2-20 of the ARID1A gene from six human cervical cancer cell lines, HeLa, SiHa, C4-1, CaSki, ME-180 and C33A, were amplified by PCR and sequenced with Sanger sequencing. ARID1A protein expression in 9 HPV-positive and 10 HPV-negative histologically confirmed cervical cancer, and two human cervical cancer cell lines, HeLa and C33A, was evaluated with immunohistochemistry. Results: A frameshift mutation was found in exon 7 (c.2274delG) in C33A, and a substitution in exon 13 (c.3471G>A) in C4-1. On the other hand, ARID1A protein expression could be detected in 8 (88.9%) of HPV-positive and 9 (90%) of HPV-negative cervical cancer. Thus, ARID1A protein positivity was not statistically different between HPV-positive and HPV-negative cervical cancer (p=0.468). However, there was difference in ARID1A protein expression between HPV-positive cervical cancer cell line HeLa and HPV-negative cervical cancer cell line C33A. ARID1A protein expression was weakly positive in the HeLa cell line but negative in the C33A cell line. Conclusions: Results in this study supported that ARID1A mutations are present in HPV-negative cervical cancer, but loss of ARID1A protein was not evident in our clinical tissue samples.