EVIDENCE THAT LOSS OF CHROMOSOME 18Q IS ASSOCIATED WITH TUMOR PROGRESSION

Four sets of cell lines (UM-SCC-14A, -14B, and -14C; UM-SCC-17A and -1 7B; UM-SCC-81A and -81B; and UM-SCC-83A and -83B), established from pr imary and metastatic or locally recurrent tumors from four patients wi th squamous cell carcinoma of the head and neck, were examined for los s of heterozygosity (LOH) on chromosome 18q. Metastatic or recurrent c ell lines from all four exhibited 18q LOH. UM-SCC-14A, -14B, and -14C, which were derived from locally recurrent (14A and 14B) and metastati c (14C) tumors, last all of 18q. However, in the other three cases, th ere was a partial loss of 18q in the recurrent or metastatic tumor cel l lines but not in the primary tumor cell lines from the same patient. To determine whether the cell lines accurately reflect in vivo loss o f 18q, we analyzed matched sets of normal, tumor, and tumor cell line DNA from eight patients with squamous cell carcinoma of the head and n eck, including the tumor tissue corresponding to UM-SCC-81B. Three of the additional seven tumors and cell lines had 18q LOH. For all eight cases in which tumor and corresponding cell line DNAs were analyzed, t here was complete concordance between allelic loss in the tumor and al lelic loss in the corresponding cell line. The common region of loss e stablished by tumors and cell lines with partial loss includes 18q21-1 8qter. This region contains the putative tumor suppressor gene DCC and two Mad (Mothers against dpp)-related genes, DPC4 and MADR2, which ar e both components in a transforming growth factor-beta-like signaling pathway. Loss of 18q in metastatic and locally recurrent tumors, but n ot in primary tumors from the same patients, suggests that a tumor sup pressor gene in this region may be important in the progression of squ amous cell carcinoma.