Genetic mechanisms in esophageal carcinogenesis: frequent deletion of 3p and 17p in premalignant lesions.
Although dysplasia of the esophagus is thought to be the precursor lesion of esophageal squamous cell carcinoma (ESC), the sequence of genetic events during esophageal carcinogenesis is unclear. Using the polymerase chain reaction, we examined allelic losses at microsatellite loci in DNAs isolated from 106 lesions among 32 patients with ESC. Allelic losses on 3p or 17p occurred frequently even in dysplastic lesions (9 of 21 and 13 of 24 samples, respectively) including lesions with mild dysplasia (3p, 4 of 10 samples; 17p, 6 of 14 samples, respectively), and allelic losses on these chromosomal arms were also observed in cancerous tissues. We also detected allelic losses of the short and long arms of chromosome 9 at a low frequency in lesions with mild dysplasia and often in lesions with severe dysplasia and in intraepithelial cancers. Our results suggested that inactivation of tumor suppressor genes on 3p and 17p occurs at a very early stage of esophageal carcinogenesis and that genes on 9p and 9q are likely to play important roles in malignant changes. Comparison of the genetic alterations in precancerous dysplastic lesions with those in carcinomas supports the idea that ESC arises from the dysplastic lesion.
Shimada
M
M
Laboratory of Molecular Medicine, University of Tokyo, Japan.
Yanagisawa
A
A
Kato
Y
Y
Inoue
M
M
Shiozaki
H
H
Monden
M
M
Nakamura
Y
Y
D000483:Alleles; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D002893:Chromosomes, Human, Pair 3; D002899:Chromosomes, Human, Pair 9; D004276:DNA, Satellite / Q000235:genetics / Q000302:isolation & purification; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D004947:Esophagus / Q000473:pathology*; D006801:Humans; D006965:Hyperplasia; D009361:Neoplasm Invasiveness; D016133:Polymerase Chain Reaction / Q000379:methods; D011230:Precancerous Conditions / Q000235:genetics* / Q000473:pathology
D004276:DNA, Satellite