Transcript map and complete genomic sequence for the 310 kb region of minimal allele loss on chromosome segment...

Molecular, functional, and clinical analyses strongly suggest that chromosome segment 11p15.5 contains a gene involved in lung cancer pathogenesis. The critical region of allele loss is 310 kb in size. We used our contig of P1-phage artificial chromosome (PAC) clones together with newly identified bacterial artificial chromosome (BAC) clones and the draft human genome sequence to complete a contiguous string of 380 407 bp. Three PAC clones that span the region were used to identify transcripts by exon trapping. Computational gene prediction algorithms were used to query the sequence for potential genes and exons. Screening for expression was performed with tissue-specific and cell line derived mRNA arrays. The region contains the complete SSA/Ro52 and RRM1 genes, exons 7-12 of the GOK gene, and the psirad pseudo-gene. A cluster of six nearly identical genes with an intact open reading frame (ORF) of 585 bp that share 75% identity with the HSPC182 gene was found. In addition, five putative novel genes were identified. Sequence tagged sites (STS) and polymorphic markers were used to screen 117 lung cancer cell lines for homozygous deletions and none were identified. These data provide the basis for the identification of a lung cancer suppressor gene on 11p15.5.