Genomic characterization of human papillomavirus-positive and -negative human squamous cell cancer cell lines

// Nene N. Kalu 1, 6 , Tuhina Mazumdar 1 , Shaohua Peng 1 , Li Shen 2 , Vaishnavi Sambandam 1 , Xiayu Rao 2 , Yuanxin Xi 2 , Lerong Li 2 , Yuan Qi 2 , Frederico O. Gleber-Netto 3 , Ameeta Patel 3 , Jing Wang 2, 4 , Mitchell J. Frederick 5 , Jeffrey N. Myers 3, 4 , Curtis R. Pickering 3, 4 and Faye M. Johnson 1, 4 1 Department of Thoracic/Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA 2 Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA 3 Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA 4 The University of Texas Graduate School of Biomedical Sciences, Houston, Texas, USA 5 Department of Otolaryngology, Baylor College of Medicine, Houston, Texas, USA 6 Current/Present address: Lonza Viral Therapy, Houston, Texas, USA Correspondence to: Faye M. Johnson, email: fmjohns@mdanderson.org Keywords: human papillomavirus, cervical cancer, head and neck squamous cell carcinoma, cell lines, mutation Received: June 22, 2017     Accepted: August 21, 2017     Published: September 21, 2017 ABSTRACT Human cancer cell lines are the most frequently used preclinical models in the study of cancer biology and the development of therapeutics. Although anatomically diverse, human papillomavirus (HPV)-driven cancers have a common etiology and similar mutations that overlap with but are distinct from those found in HPV-negative cancers. Building on prior studies that have characterized subsets of head and neck squamous cell carcinoma (HNSCC) and cervical squamous cell carcinoma (CESC) cell lines separately, we performed genomic, viral gene expression, and viral integration analyses on 74 cell lines that include all readily-available HPV-positive (9 HNSCC, 8 CESC) and CESC (8 HPV-positive, 2 HPV-negative) cell lines and 55 HPV-negative HNSCC cell lines. We used over 700 human tumors for comparison. Mutation patterns in the cell lines were similar to those of human tumors. We confirmed HPV viral protein and mRNA expression in the HPV-positive cell lines. We found HPV types in three CESC cell lines that are distinct from those previously reported. We found that cell lines and tumors had similar patterns of viral gene expression; there were few sites of recurrent HPV integration. As seen in tumors, HPV integration did appear to alter host gene expression in cell lines. The HPV-positive cell lines had higher levels of p16 and lower levels of Rb protein expression than did the HPV-negative lines. Although the number of HPV-positive cell lines is limited, our results suggest that these cell lines represent suitable models for studying HNSCC and CESC, both of which are common and lethal.