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 numerou s complex chromosome abnormalities. To make sense of this complexity i t is necessary to identify the consistent chromosome changes in a larg e panel of tumors, to determine if these changes are true representati ons of the in vivo situation, and to construct a map of gene loci like ly to be involved in the development and progression of cancer. Our fi ndings indicate that cultured tumor cells are cytogenetically stable w hen compared to cells evolving in vivo. We also found that clues to th e sequence of events in clonal evolution of individual tumors can be d educed 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 ident ification 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, gp, and 18q. Les s common consistent changes found in 30-40% of tumors are gains affect ing 3q, 5p, 7p, 8q, and llq. Preliminary evidence suggests that loss o f 18q may be prognostically important and may involve disruption of ge nes encoding cell adhesion molecules. (C) 1993 Wiley-Liss, Inc.