Genomic instability in squamous cell carcinoma of the head and neck.
The role of genomic instability in the development of squamous cell carcinoma (SCCHN) has become apparent with the publication of three major allelotype analysis of this disease, as well as many publications which have concentrated on specific target regions. The measurement of accumulated genetic alterations or fractional allele loss, as determined by allelotype analysis, provides a useful molecular indicator of tumour behaviour. In one major study, a positive correlation was found between FAL > median value and lymph node metastasis and also with a poor clinical outcome. In addition the recognition of microsatellite instability as a marker of DNA repair defects has provided a further molecular marker of the disease process and that loss of heterozygosity analysis and microsatellite instability appear to be independent genetic events in the development of SCCHN. Furthermore, the recognition of a number of novel target regions in SCCHN on chromosome arms, 1 p, 3p, 8p, 9p, 13q, 17p and 18q and our understanding of the role of certain oncogenes and tumour suppressor genes and their interaction with human papillomavirus has provided further elucidation of the neoplastic process. Even though this review describes a number of molecular events in SCCHN, the sequence of events still eludes the scientific community at present.
Field
J K
JK
Molecular Genetics and Oncology Group, University of Liverpool, U.K.
D000483:Alleles; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D018895:Microsatellite Repeats; D009857:Oncogenes