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Frequent Loss of Heterozygosity in Region of the KIP1 Locus in Non-Small Cell Lung Cancer: Evidence for a New Tumor Suppressor Gene on the Short Arm of Chromosome 12¹

Division of Hematology/Oncology, Cedars-Sinai Research Institute, University of California at Los Angeles School of Medicine, Los Angeles, California 90048 [S. T., N. M., M. K., J. S., S. P., C. W. M., H. P. K.], and Department of Internal Medicine, Kochi Medical School, Kochi, Japan [I. M.]

To refine the chromosomal localization of a putative tumor suppressor gene, we analyzed the loss of heterozygosity (LOH) of chromosome 12 in 36 primary non-small cell lung cancer (NSCLC) samples with matched normal DNA using 22 highly informative polymorphic markers. Twelve cases showed LOH at one or more loci on chromosome 12. LOH of chromosome arm 12p was more frequent in large cell carcinoma than squamous cell carcinoma, indicating molecular genetic heterozygosity within the major NSCLC subtypes. We identified the smallest commonly deleted region on chromosome 12p13. This region is flanked by D12S269 and D12S308, including the KIP1 gene. Mutational analysis of KIP1 using PCR-single strand conformation polymorphism and Southern Blot analysis showed no homozygous deletions, rearrangements, or point mutations, suggesting that the altered gene in this region is not the KIP1 gene. These data suggest that a new tumor suppressor gene which is involved in tumorigenesis of NSCLC is in the region of KIP1.

¹ Supported in part by NIH Grants DK42792 and CA42710, the Concern Foundation, the Parker Hughes Trust, and the Louis Shushan Fund.

² To whom requests for reprints should be addressed, at Cedars-Sinai Medical Center, UCLA School of Medicine, 8700 Beverly Boulevard, B208, Los Angeles, CA 90048. Phone: (310) 855-4609; Fax: (310) 659-9741.

Received 11/ 2/95. Accepted 12/28/95.

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