Chromosomal biomarkers in the clonal evolution of head and neck squamous neoplasia.
The biological behavior of any tumor is the result of changes in gene expression caused by mutations accumulated in the carcinogenic process. In squamous carcinoma of the head and neck (SCCHN) there are numerous complex chromosome abnormalities. To make sense of this complexity it is necessary to identify the consistent chromosome changes in a large panel of tumors, to determine if these changes are true representations of the in vivo situation, and to construct a map of gene loci likely to be involved in the development and progression of cancer. Our findings indicate that cultured tumor cells are cytogenetically stable when compared to cells evolving in vivo. We also found that clues to the sequence of events in clonal evolution of individual tumors can be deduced by studying primary and metastatic tumors from the same patient, by examining separate clones within the same tumor, and by analyzing ploidy changes. Furthermore, comparison of the in vitro karyotypes to in situ analysis of the tumor tissue indicates that in vitro cultures are good representations of the in vivo tumor. We conclude that identification of consistent chromosome changes in cultured cells can lead to the loci of genes important in the clinical behavior of individual tumors. The most frequent chromosome abnormalities in SCCHN, found in 40-60% of tumors, are deletions affecting 3p, 5q, 8p, 9p, and 18q. Less common consistent changes found in 30-40% of tumors are gains affecting 3q, 5p, 7p, 8q, and 11q. Preliminary evidence suggests that loss of 18q may be prognostically important and may involve disruption of genes encoding cell adhesion molecules.
Carey
T E
TE
Department of Otolaryngology/Head and Neck Surgery, University of Michigan Cancer Center, Ann Arbor 48109-0506.
Worsham
M J
MJ
Van Dyke
D L
DL
D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002869:Chromosome Aberrations; D002999:Clone Cells; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D007621:Karyotyping