Homozygous deletion at chromosome 2q33 in human small-cell lung carcinoma identified by arbitrarily primed PCR genomic fingerprinting.

We have searched for novel genetic alterations in human cancer cell lines by using the arbitrarily primed polymerase chain reaction (AP-PCR), which is a PCR-based genomic fingerprinting. A homozygous deletion was detected in a small-cell lung carcinoma (SCLC) cell line, NCI-H82. Since homozygous deletion is a critical genetic alteration for the inactivation of tumor suppressor gene, we defined the locus of homozygous deletion. Fluorescence in situ hybridization analysis revealed that the deletion was localized at chromosome 2q33. Allelic loss on chromosome 2q was detected in 29.4% (5/17) of SCLC and 37.5% (12/32) one non-SCLC by restriction fragment length polymorphism analysis. Considerably high incidence of allelic loss on chromosome 2q was also detected in colorectal carcinoma and neuroblastoma. These results suggest the presence of a novel tumor suppressor gene at 2q33, which is involved in the development of several human cancers. The size of the homozygous deletion in the NCI-H82 cell line was more than 20 kilobase pairs. Seven loci mapped to 2q32-qter were all retained in this cell line, suggesting the presence of submicroscopic interstitial deletion in this cell line. Homozygous deletion detected in this study should be an invaluable tool for positional cloning of the target tumor suppressor gene at 2q33.