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Chromosome 3p Deletions in Head and Neck Carcinomas: Statistical Ascertainment of Allelic Loss¹

Laboratory of Immunobiology [F.L., G. G., M.L.O., M.L.]., Data Management Services, Inc. [M.F.], and Program Resources, Inc./DynCorp, National Cancer Institute-Frederick Cancer Research and Development Center Frederick, Maryland 21702-1201 [K.T., K.H., J.D.]; and the Department of Radiation Oncology, University of Chicago Medical Center, Chicago, Illinois 60637 [J.C., M.B., R.W.]

Loss of function of tumor suppressor genes is important in the origin and progression of common adult tumors. Loss of heterozygosity indicating allelic loss has been used to detect chromosomal regions that harbor these genes. Using over 20 restriction fragment length polymorphism markers spaced throughout the entire length of chromosome 3p, we have generated 3p allelotypes for 18–26 head and neck squamous cell carcinoma cell lines. We then estimated the average heterozygosity over 19 loci for a random sample drawn from natural populations to be 7.80 and that for the tumor lines to be 1.65, indicating a gross reduction of heterozygosity, presumably due to allelic loss. Further comparison of per locus heterozygosity in normal and tumor DNAs showed which loci contributed to the general loss of heterozygosity. We showed that the commonly deleted region of 3p probably lies telomeric to D3S3 (3p14) and centromeric to RAF1 (3p25). This large region includes several putative tumor suppressor genes involved in multiple common tumor types of lung, breast, kidney, ovary, and cervix. The data demonstrate that chromosome 3p allelic loss is a common event in head and neck cancers and suggest that chromosome 3p tumor suppressor genes contribute to the pathogenesis of these tumors.

¹ This project has been funded at least in part with Federal funds from the Department of Health and Human Services under Contracts NO1-CO-74102 (K.T., K.H., J.D.), NO1-CO-74103 (M.F.), and CA 41 068 (R.W.). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the United States Government.

² To whom requests for reprints should be addressed, at the Laboratory of Immunobiology, National Cancer Institute, Frederick Cancer Research and Development Center, Building 560, Room 12-71, Frederick, MD 21702-1201.

Received 9/16/91. Accepted 1/ 8/92.

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