Genomic characterization of clonal evolution during oropharyngeal carcinogenesis driven by human papillomavirus 16

• Published in: BMB reports Vol. 51; no. 11; pp. 584 - 589
• Main Authors: Chae, Jeesoo, Park, Weon Seo, Kim, Min Jung, Jang, Se Song, Hong, Dongwan, Ryu, Junsun, Ryu, Chang Hwan, Kim, Ji-Hyun, Choi, Moon-Kyung, Cho, Kwan Ho, Moon, Sung Ho, Yun, Tak, Kim, Jong-Il, Jung, Yuh-Seog
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Society for Biochemistry and Molecular Biology 01.11.2018; 생화학분자생물학회
• Subjects: Carcinogenesis - genetics; Carcinogenesis - pathology; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - virology; Case-Control Studies; Cell Transformation, Viral - genetics; Cell Transformation, Viral - physiology; Clonal Evolution - genetics; DNA Copy Number Variations; DNA Mutational Analysis - methods; Female; Gene Frequency; Genome-Wide Association Study; Genomics; Human papillomavirus 16 - physiology; Humans; Middle Aged; Mouth Mucosa - pathology; Mouth Mucosa - virology; Oropharyngeal Neoplasms - genetics; Oropharyngeal Neoplasms - pathology; Oropharyngeal Neoplasms - virology; Sequence Analysis, DNA; Squamous Cell Carcinoma of Head and Neck - genetics; Squamous Cell Carcinoma of Head and Neck - pathology; Squamous Cell Carcinoma of Head and Neck - virology; 화학
• ISSN: 1976-6696; 1976-670X
• DOI: 10.5483/BMBRep.2018.51.11.091

Secondary prevention via earlier detection would afford the greatest chance for a cure in premalignant lesions. We investigated the exomic profiles of non-malignant and malignant changes in head and neck squamous cell carcinoma (HNSCC) and the genomic blueprint of human papillomavirus (HPV)-driven carcinogenesis in oropharyngeal squamous cell carcinoma (OPSCC). Whole-exome (WES) and whole-genome (WGS) sequencing were performed on peripheral blood and adjacent non-tumor and tumor specimens obtained from eight Korean HNSCC patients from 2013 to 2015. Next-generation sequencing yielded an average coverage of 94.3× for WES and 35.3× for WGS. In comparative genomic analysis of non-tumor and tumor tissue pairs, we were unable to identify common cancer-associated early mutations and copy number alterations (CNA) except in one pair. Interestingly, in this case, we observed that non-tumor tonsillar crypts adjacent to HPV-positive OPSCC appeared normal under a microscope; however, this tissue also showed weak p16 expression. WGS revealed the infection and integration of high-risk type HPV16 in this tissue as well as in the matched tumor. Furthermore, WES identified shared and tumor-specific genomic alterations for this pair. Clonal analysis enabled us to infer the process by which this transitional crypt epithelium (TrCE) evolved into a tumor; this evolution was accompanied by the subsequent accumulation of genomic alterations, including an ERBB3 mutation and large-scale CNAs, such as 3q27-qter amplification and 9p deletion. We suggest that HPV16-driven OPSCC carcinogenesis is a stepwise evolutionary process that is consistent with a multistep carcinogenesis model. Our results highlight the carcinogenic changes driven by HPV16 infection and provide a basis for the secondary prevention of OPSCC. [BMB Reports 2018; 51(11): 584-589].