title: Genetic aberrations in squamous cell carcinoma of the head and neck (SCCHN), with reference to oral carcinoma (review).
abstract: Squamous cell carcinoma of the head and neck (SCCHN) arises as a consequence of multiple molecular events induced by the effects of various habits such as tobacco and use of alcoholic beverages, influenced by environmental factors, possibly viruses in some instances, against a background of heritable resistance or susceptibility. Oral squamous cell cancers have a similar aetiology. Genetic damage affects many chromosomes and genes, including oncogenes and tumour suppressor genes, and it is the accumulation of such genetic damage, possibly along with an impaired ability to repair this damage - an inherited trait in some cases - that appears to lead to carcinoma in some instances, sometimes via a clinically evident pre-malignant, or potentially malignant, lesion. This communication reviews the advances in the understanding of this complex and rapidly developing area of research over the past decade. Cytogenetic and molecular analyses have shown changes in several chromosomes in oral cancer, particularly in chromosomes 3, 9, 11, 13 and 17. Analyses of allelic losses has allowed for the identification of chromosomal regions harbouring tumour suppressor genes (TSGs). Impaired function of such genes or their products, or activation of oncogenes, or both, may be involved in carcinogenesis. Probably the most significant findings thus far have been in relation to TSGs with the discovery of p53 mutations on chromosome 17 as in many other tumours, indicating disturbed function of this TSG and some on chromosomes 3 and 9 (MTS-1) which may be of comparable or greater significance. Over-expression of oncogenes, especially those on chromosome 11 (PRAD-1, Int-2, hst-l, and bcl-1 in particular) has also been implicated in carcino-genesis. The analysis of microsatellite instability (MI or RER, replication error repair) in tumour specimens, which are associated with defects in DNA repair genes has provided a further method of assessing genetic damage in the genome of sporadic cancers. Microsatellite instability (MI) has been demonstrated in several carcinomas as well as SCCHN. These research findings have now reached the stage where it is becoming possible to begin to introduce them into clinical practice for the more sensitive detection of potentially malignant lesions, better diagnosis and prognostication, and hopefully, to start to develop novel therapies such as gene therapy.
authors.affiliation: UNIV LIVERPOOL,DEPT CLIN DENT SCI,MOL GENET & ONCOL GRP,LIVERPOOL L69 3BX,MERSEYSIDE,ENGLAND.
authors.forename: C
authors.initials: C
authors.lastname: Scully
authors.forename: J
authors.initials: J
authors.lastname: Field