Delineating an epigenetic continuum in head and neck cancer

Abstract

A tissue field of somatic genetic alterations precedes the histopathological phenotypic changes of carcinoma. Genomic changes could be of potential use in the diagnosis and prognosis of pre-invasive squamous head and neck carcinoma (HNSCC) lesions and as markers for cancer risk assessment. Studies of sequential molecular alterations and genetic progression of preinvasive HNSCC have not been clearly defined. Studies have shown recurring alterations at chromosome 9p21 (location of the CDKN2A) and TP53 mutations in the early stages of HNSCC. However, gene silencing via hypermethylation is still a relatively new idea in the development of HNSCC and little is known about the contribution of epigenetics to the development of neoplasia, its transformation, progression, and recurrence in HNSCC. This review examines the role of promoter hypermethylation of tumor suppressor genes in the progression continuum from benign papillomas to malignancy in HNSCC.

A Poor Prognosis Subtype of HNSCC Is Consistently Observed across Methylome, Transcriptome, and miRNome Analysis

“…Many of these genes were already known to be involved in important functions, including apoptosis, the cell cycle, cell migration, and invasion (for reviews see refs. 28,29). Interestingly, a recent analysis has shown that a protein involved in cell adhesion (cadherin 11) is specifically methylated in metastases (30).…”

HPV-related methylation signature predicts survival in oropharyngeal squamous cell carcinomas

“…Aberrant DNA hypermethylation within gene promoters is a hallmark in various human malignancies, including HNSCC (15)(16)(17), and usually results in downregulation of the associated genes. However, gene silencing via gene promoter methylation is still a novel concept to explain the development of HNSCC; in particular, its effect on the pathogenesis of HPV-driven OPSCC as Supplemental Tables 22 and 23).…”

IGSF4Methylation as an Independent Marker of Human Papillomavirus–Positive Oropharyngeal Squamous Cell Carcinoma

“…Our group has demonstrated, using high-throughput methods, the contribution of both genetic 1 1 , 1 2 and epigenetic events, 1 3 often working together, 14 in the development and progression of HNSCC. 15 The goal of our study was to examine the status of HPV16 infection and methylation status of IGSF4, DAPK1, and ESR1, candidate genes associated with HNSCC pathogenesis, 14,15 in an OPSCC cohort. 16 …”