Tumor Progression Evidence That Loss of Chromosome 18q Is Associated with

Four sets of cell lines (UM-SCC.14A, -14B, and -14C; UM-SCC-17A and .17B; UM-SCC.81A and -SiB; and UM-SCC.83A and -83B), estab lished from primary and metastatic or locally recurrent tumors from four patients with squamous cell carcinoma of the head and neck, were exam med for loss of heterozygosity (LOH) on chromosome lSq. Metastatic or recurrent cell lines from all four exhibited 18q LOH. UM-SCC-14A, -14B, and -14C, which were derived from locally recurrent (14A and 14B) and metastatic (14C) tumors, lost all of lSq. However, in the other three cases, there was a partial loss of 18q in the recurrent or metastatic tumor cell lines but not in the primary tumor cell lines from the same patient. To determine whether the cell lines accurately reflect in vivo loss of 18q, we analyzed matched sets of normal, tumor, and tumor cell line DNA from eight patients with squamous cell carcinoma of the head and neck, includ ing the tumor tissue corresponding to UM-SCC-81B. Three of the addi tional seven tumors and cell lines had lSq LOH. For all eight cases in which tumor and corresponding cell line DNAs were analyzed, there was complete concordance between allelic loss in the tumor and allelic loss in the corresponding cell line. The common region of loss established by tumors and cell lines with partial loss includes 18q21—l8qter. This region contains the putative tumor suppressor gene DCC and two Mad (@othera @gainst@$pp)-relatedgenes, DPC4 and MI4.DR2,which are both compo nents in a transforming growth factor-fl-like signaling pathway. Loss of lSq in metastatic and locally recurrent tumors, but not in primary tumors from the same patients, suggests that a tumor suppressor gene in this region may be important in the progression of squamous cell carcinoma.