Detailed deletion mapping suggests the involvement of a tumor suppressor gene at 17p13.3, distal to p53, in the pathogenesis of lung cancers.
The short arm of chromosome 17 is one of the most frequently affected chromosomal regions in lung cancers, while there is solid evidence that the p53 gene at 17p13.1 is a target for frequent 17p deletions. In the present study, we re-evaluated 17p deletions in lung cancers by conducting a detailed analysis of the minimum deleted region(s) on 17p with reference to the p53 gene status in each 100 primary lung cancer cases. In addition to the p53 locus at 17p13.1, the presence of an independent, commonly deleted region(s) at 17p13.3 was identified. Furthermore, loss of heterozygosity (LOH) at 17p13.3 was shown to be even more frequent than that at 17p13.1 and it appeared to occur in the absence of p53 mutation and/or 17p13.1 deletion. These results suggest that in addition to the p53 gene at 17p13.1, an as yet unidentified tumor suppressor gene(s) residing at 17p13.3 might play a role in lung carcinogenesis possibly in an earlier phase than the p53 gene. This would warrant future studies to identify the putative tumor suppressor gene at 17p13.3 in order to gain a better understanding of the molecular pathogenesis of this fatal disease.
Konishi
H
H
Laboratory of Ultrastructure Research, Aichi Cancer Center Research Institute, Nagoya, Japan.
Takahashi
T
T
Kozaki
K
K
Yatabe
Y
Y
Mitsudomi
T
T
Fujii
Y
Y
Sugiura
T
T
Matsuda
H
H
Takahashi
T
T
Takahashi
T
T
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D018287:Carcinoma, Large Cell / Q000235:genetics / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000235:genetics / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D016158:Genes, p53; D006801:Humans; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D017384:Sequence Deletion