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Evidence That Loss of Chromosome 18q Is Associated with Tumor Progression¹

Laboratory of Head and Neck Cancer Biology [C. J. F., T. E. C.], Department of Otolaryngology/Head and Neck Surgery, and the Department of Pathology [K. D. M., K. O. D.], University of Michigan, Ann Arbor, Michigan 48109-0506

Four sets of cell lines (UM-SCC-14A, -14B, and -14C; UM-SCC-17A and -17B; UM-SCC-81A and -81B; and UM-SCC-83A and -83B), established from primary and metastatic or locally recurrent tumors from four patients with squamous cell carcinoma of the head and neck, were examined for loss of heterozygosity (LOH) on chromosome 18q. 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 18q. 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, 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, 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 18q21-18qter. This region contains the putative tumor suppressor gene DCC and two Mad (Mothers against dpp)-related genes, DPC4 and MADR2, which are both components in a transforming growth factor-ß-like signaling pathway. Loss of 18q 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.

¹ This study was supported by grants from the John and Suzanne Munn Endowment to the University of Michigan Cancer Center, United States Public Health Service NIH Grant CA-28564, General Clinical Research Center Grant MO1-RR00042, and summer research fellowships from the Howard Hughes Medical Institute.

² Present address: Department of Pathology, Scritch School of Medicine, Loyola University Chicago, Maywood, IL 60153.

³ To whom requests for reprints should be addressed, at Laboratory of Head and Neck Cancer Biology, 6020 Kresge Hearing Research Institute, P. O. Box 0506, 1301 East Ann Street, Ann Arbor, MI 48109-0506. Phone: (313) 764-4371; Fax: (313) 764-0014.

Received 8/19/96. Accepted 1/11/97.

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