Oncogenes and tumour-suppressor genes in squamous cell carcinoma of the head and neck.
Cancer is now considered to be a multi-hit process which involves a number of aberrant genetic events culminating in malignant transformation. In squamous cell carcinoma (SCC) of the head and neck the action of both oncogenes and tumour-suppressor genes has been identified during the course of the disease. Cytogenetic analysis of these carcinomas has demonstrated chromosomal breakpoints, particularly in the regions of 1p22 and 11q13 together with frequent amplification of the proto-oncogenes in the 11q13 amplicon; int-2, hst-1 and bcl-1. Ras mutations have been infrequently identified in the Western World whereas ras over-expression has been a common finding and may be associated with the early development of head and neck cancer. C-myc over-expression appears to correlate with a poor prognosis for these patients. The tumour-suppressor gene p53 is also thought to be involved in the development of SCC in head and neck tumours and its aberrant expression is associated with a history of heavy smoking and heavy drinking. E-cadherin, a putative tumour-suppressor gene is down-regulated in poorly differentiated head and neck SCC and maybe important in nodal metastasis. A recent study has indicated that the Human Papilloma Virus (HPV 16 and 33) has a role in the aetiology of tonsillar carcinomas and HPV has been shown to produce transforming proteins which bind to and inactivate the p53 tumour suppressor gene. This evidence suggests that the possibility of a viral mechanism for the development of SCC in the head and neck should be considered. This paper proposes a series of genetic events to explain the development of SCC of the head and neck.
Field
J K
JK
School of Dentistry, University of Liverpool.
D015820:Cadherins / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002472:Cell Transformation, Viral; D002880:Chromosomes, Human, Pair 11; D004263:DNA Tumor Viruses / Q000472:pathogenicity; D066246:ErbB Receptors; D005784:Gene Amplification; D016147:Genes, Tumor Suppressor; D016259:Genes, myc; D016158:Genes, p53; D011905:Genes, ras; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D027383:Papillomaviridae / Q000472:pathogenicity; D011519:Proto-Oncogenes
D015820:Cadherins; D066246:ErbB Receptors