Accumulation of genetic alterations during esophageal carcinogenesis.
Using polymerase chain reaction amplification of microsatellite regions in DNA from 11 epithelial dysplasias of the esophagus and 21 early squamous cell carcinomas, we were able to detect frequent loss of heterozygosity (LOH) on chromosomes 3p21.3 and 9q31 even in low-grade dysplasias. In contrast, we observed frequent LOHs on chromosomes 9p22 and 17p13 (TP53 locus) only in high-grade dysplasias and carcinomas, but not in any low-grade dysplasias. Analysis of LOH at the same four chromosomal regions in DNA of five additional minimal carcinomas and accompanying dysplastic lesions revealed loss of alleles at the loci on 3p21.3 and 9q31 throughout various degrees of dysplasia and carcinoma; again, LOHs on 9p22 and 17p13 occurred only in high-grade dysplasia and carcinoma in situ. Our results indicated that inactivation of putative tumor suppressor genes on 3p21.3 and 9q31 may be early genetic events during esophageal carcinogenesis, and that additional genetic alterations on 9p22 and 17p13 probably play roles in progression.
Mori
T
T
Department of Biochemistry, Toshima-ku, Tokyo, Japan.
Yanagisawa
A
A
Kato
Y
Y
Miura
K
K
Nishihira
T
T
Mori
S
S
Nakamura
Y
Y
D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17; D002893:Chromosomes, Human, Pair 3; D002899:Chromosomes, Human, Pair 9; D004273:DNA, Neoplasm / Q000032:analysis; D004276:DNA, Satellite / Q000032:analysis; D004938:Esophageal Neoplasms / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D016133:Polymerase Chain Reaction
D004273:DNA, Neoplasm; D004276:DNA, Satellite