Three New Regions on Chromosome 17p13.3 Distal to p53 with Possible Tumor Suppressor Gene Involvement in Lung Cancer

Abstract

We investigated loss of heterozygosity (LOH) at the distal portion of the p53 gene on the short arm of chromosome 17 in lung cancers in order to search for new tumor suppressor genes. The roles of the putative genes were also studied in terms of pathological features. One hundred and forty-five resected non-small cell lung cancers were examined for LOH using 11 markers mapped on, and distal to the p53 locus, and deletion maps were constructed. Four commonly deleted regions were found: one from TP53 to ENO3, where the p53 gene resides, and three others from ENO3 to D17S1566, D17S379 to D17S1574 and distal to ABR, with LOH frequencies almost the same as, or higher than, at the TP53 locus. Examination of the relationship between LOH of the latter three regions and histopathological parameters of adenocarcinomas (genetically negative for p53 mutation) revealed allelic losses on D17S379 to be associated with advanced lesions, while D17S513 was more frequently deleted in poorly differentiated tumors. These results indicate that new tumor suppressor gene(s) may reside on these three distinctly deleted regions on chromosome 17p13.3 distal to the p53 gene in lung cancer, with possible roles in progression and differentiation of adenocarcinomas.

Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers

“…Third, high frequency of LOH at 17p13.3 and relatively low frequency of TP53 mutation in cases of hepatocellular carcinomas, lung cancers, and astrocytomas indicate the presence of other TS genes involved in the development of these tumors. We have found that one minimal LOH region described in hepatocellular carcinoma and located telomeric to TP53 between markers D17S1866 and D17S1574 harbor three miRs: miR-22, miR-132, and miR-212 (29), whereas between ENO3 and TP53, we found miR-195 (30). Fourth, homozygous deletions (HDs) in cancer suggest the presence of TS genes (31) and several miR genes are located in homozygously deleted regions without known TS genes.…”

OVCA2 is downregulated and degraded during retinoid‐induced apoptosis

“…15,16,38 In addition, LOH at 17p13.3 is more frequent than at 17p13.1, where TP53 maps, and it appeared to occur in the absence of TP53 mutation and/or 17p13.1 dele- tion. 15,16,38 It will be important to investigate further the role of OVCA1 in the development of lung cancer. In addition, it will be of interest to analyze the effect that RA and 4HPR have on OVCA1 expression in breast and ovarian cell lines.…”

MicroRNAs and chromosomal abnormalities in cancer cells

“…High frequency of LOH at 17p13.3 and relatively low frequency of TP53 mutation in cases of hepatocellular carcinomas (HCC), lung cancers and astrocytomas indicate the presence of other TSGs involved in the development of these tumors. We have found that one minimal LOH region described in HCC and located telomeric to TP53 (tumor protein p53) gene between markers D17S1866 and D17S1574 (Zhao et al, 2003) harbor three miRNAs: miR-22, miR-132 and miR-212, while between ENO3 and TP53 (Tsuchiya et al, 2000) we found miR-195 (Calin et al, 2004b).…”