Detailed characterization of a homozygously deleted region corresponding to a candidate tumor suppressor locus at 21q11-21 in human lung cancer.

The frequent presence of loss of heterozygosity (LOH) at 21q21 in lung cancer suggests the existence of putative tumor suppressor genes in this genomic region. Furthermore, the identification of a homozygous deletion in this region has lent further support for its potential involvement in pathogenesis. In the present study, extensive screening of a large panel of lung cancer cell lines resulted in the identification of a homozygous deletion at 21q21.1 in the large cell lung carcinoma cell line Calu-6. Subsequent detailed characterization allowed us to narrow down the extent of the shortest region of overlap of homozygous deletions at 21q21.1 to 3.4 Mbp. Together with existing information showing a relationship with the shortest region of overlap and LOH in lung cancer, the overlapping 1.8-Mbp region was suggested to be a prime candidate for a genomic region that may harbor putative tumor suppressor genes. We found frequent downregulation of two coding genes, SAMSN1 and USP25, as well as of three miRNA genes, miR-99a, let-7c, and miR-125b-2, which reside in the commonly deleted region in human lung cancer. In addition, initial attempts were made to investigate their potential alterations and functional involvements in the development of lung cancer.