Deletions of 17p are associated with transition from early to advanced colorectal cancer.
Several chromosome defects parallel morphologic evolution in colorectal tumor progression. Allelic losses in the short arm of chromosome 17, the majority encompassing the 17p13.3 band, have been found in advanced cancer in the absence of TP53 mutations, suggesting that loss of genes in this chromosome region is relevant for tumorigenesis. The aim of this study was to investigate 17p13.3 deletions throughout the colorectal tumor progression using two-color fluorescence in situ hybridization. Histologic sections from 20 colorectal adenomas containing early invasive carcinoma were analyzed by interphase fluorescence in situ hybridization using a centromeric probe for chromosome 17 simultaneously with a subtelomeric probe mapping to the 17p13.3 band. Separate evaluation was made for sectors corresponding to adenoma tissue with low-grade dysplasia, high-grade dysplasia, and early cancer. The same technique was also used in 20 cases of advanced adenocarcinoma of the large bowel. Loss of one centromeric signal was observed in 20, 40, 50, and 10% of low-grade dysplasia, high-grade dysplasia, early cancer, and advanced cancer, respectively (P<0.02 early vs. advanced cancer). Subtelomeric 17p deletions were seen in 60% of advanced cancer and in 15% of early cancer (P<0.01). These findings indicate that loss of genes from the 17p13.3 chromosome region may play an important role in sustaining the transition from early to advanced cancer in colorectal tumor progression.
Risio
Mauro
M
Unit of Pathology, Institute for Cancer Research and Treatment, Strada Provinciale 142, Km. 3.95, 10060, Candiolo, Torino, Italy. mrisio@mauriziano.it
Casorzo
Laura
L
Chiecchio
Laura
L
De Rosa
Giovanni
G
Rossini
Francesco Paolo
FP
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D016158:Genes, p53; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007413:Intestinal Mucosa / Q000473:pathology; D009154:Mutation; D009367:Neoplasm Staging; D012004:Rectal Neoplasms / Q000235:genetics* / Q000473:pathology; D012811:Sigmoid Neoplasms / Q000235:genetics* / Q000473:pathology