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Analysis of copy number changes suggests chromosomal instability in a minority of large colorectal adenomas
Author(s) -
Jones AM,
Thirlwell C,
Howarth KM,
Graham T,
Chambers W,
Segditsas S,
Page KM,
Phillips RKS,
Thomas HJW,
Sieber OM,
Sawyer EJ,
Tomlinson IPM
Publication year - 2007
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2234
Subject(s) - comparative genomic hybridization , chromosome instability , biology , chromosome , snp array , genome instability , genetics , cytogenetics , snp , copy number variation , single nucleotide polymorphism , gene , dna , genome , genotype , dna damage
We have examined chromosomal‐scale mutations in 34 large colorectal adenomas (CRAs). A small number of changes (median = 2, IQR = 0–4) were found by array‐comparative genomic hybridization (aCGH) in most tumours. The most common changes were deletions of chromosomes 1p, 9q, 17, 19, and 22, and gains of chromosomes 13 and 21. SNP‐LOH analysis and pseudo‐digital SNP‐PCR analysis detected occasional copy‐neutral LOH. Some aCGH changes found frequently in colorectal carcinomas, such as deletions of chromosomes 4q and 18q, were very infrequent in the adenomas. Almost all copy number changes were of small magnitude, far below the predicted levels even for single copy gain/loss; investigation suggested that these changes were either artefactual or occurred in sub‐clones within the tumours. In some cases, these sub‐clones may have represented progression towards carcinoma, but comparison with aCGH data from carcinomas showed this to be unlikely in most cases. In two adenomas, there was evidence of a large, outlying number of copy number changes, mostly resulting from part‐chromosome deletions. Overall, moreover, there was evidence of a tendency towards part‐chromosome deletions—consistent with chromosomal instability (CIN)—in about one‐sixth of all tumours. However, there was no evidence of CIN in the form of whole‐chromosome copy number changes. Our data did not support previous contentions that CRAs tend to show chromosome breakage at fragile sites owing to CIN associated with an elevated DNA damage response. Chromosomal‐scale mutations occur in some CRAs; although CIN is not the norm in these lesions, it probably affects a minority of cases. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.