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 pre-invasive 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.

Keywords: Benign papillomas; DNA hypermethylation; Progression; Squamous cell carcinoma.

Figure 1. A postulated hypothetical epigenetic progression model

DNA hypermethylation of CDKN2B, CDKN2A, APC, BRCA2, DAPK1, HIC1, TP73, and ESR1 suggest early events in the tumorigenesis continuum from benign to primary SCC. CDH13, CHFR, IGSF4, and RARB (bolded) appear to be primary tumor-specific events and KLK10 and FHIT progression to metastasis-specific events.