Chromosomal gains and losses in primary colorectal carcinomas detected by CGH and their associations with tumour DNA ploidy, genotypes and phenotypes

Angelis, P. De; Clausen, O. P. F.; Schjølberg, Aasa R.; Stokke, Trond

doi:10.1038/sj.bjc.6690388

Cited by 140 publications

(172 citation statements)

References 53 publications

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“…3,4,17 The reason for such an association remains to be discovered. However, we and De Angelis et al 13 found an inverse relationship between chromosome 4 loss and reduced apoptosis.…”

Section: Discussioncontrasting

confidence: 53%

“…4,[18][19][20] Loss of chromosome arm 9p is not an infrequent event in colorectal cancer. 13,21 We identified a significant association between 9p loss and high Bold represents values which are statistically significant.…”

Section: Discussionmentioning

confidence: 82%

“…Overall, the chromosomal aberrations described here are consistent with chromosomal changes previously reported for colorectal cancer. [10][11][12][13] Although the number of genomic aberrations may potentially substitute for chromosomal instability, it was paramount to establish the MSI status of the tumours because it could have had a profound impact on the analysis of disease-free survival. It is well established that cancers with high microsatellite instability have better survival than microsatellite stable tumours.…”

Section: Discussionmentioning

confidence: 99%

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Genetic profiling of stage I and II colorectal cancer may predict metastatic relapse

et al. 2006

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A substantial number of patients with early-stage colorectal cancer relapse from metastatic disease. Identification of these patients by genetic profiling of their primary tumours may allow more informed followup and tailored administration of adjuvant therapy. Primary tumours from 70 patients with early-stage and largely microsatellite-stable colorectal cancer were profiled using metaphase-based comparative genomic hybridization (CGH) and the aberrations confirmed independently in a subset of patients using microarraybased CGH. Of the 70 cancers, 61 were amenable to CGH, and follow-up data was available from 56 patients. Genomic aberrations were correlated with patients' survival using univariate, multivariate and Kaplan-Meier survival curves. Metastatic primary tumours exhibited more complex genomic aberrations than non-metastatic primary tumours. Loss of chromosome 4p was an independent prognostic factor in early-stage colorectal cancer using multivariate analysis (Hazard ratio, 9.6; 95% CI, 3.3-28; P ¼ 0.0001). Loss of both chromosome arms 8p and 18q had a statistically significant negative effect on disease-free survival. Moreover, primary tumours with loss of both chromosomes 4 and 14q bestowed poorer prognosis than tumours with loss of any one of the two chromosomes (Po0.0001). Genetic profiling of primary tumours of patients with early-stage colorectal cancer is of significant value in identifying the subset of patients who may relapse with metastatic disease. Accordingly, the molecular genetic features of primary tumours should be considered in the mainstream management of patients with this specific stage of the disease.

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“…3,4,17 The reason for such an association remains to be discovered. However, we and De Angelis et al 13 found an inverse relationship between chromosome 4 loss and reduced apoptosis.…”

Section: Discussioncontrasting

confidence: 53%

Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

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Genetic profiling of stage I and II colorectal cancer may predict metastatic relapse

et al. 2006

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“…[21][22][23][24] CGH studies on both colorectal adenomas and carcinomas have also confirmed the gain of chromosome 7 material as a frequent change. 11,12,25,26 Ried et al 12 demonstrated gain of chromosome 7 material in 4 of 12 in what they described as high-grade adenomas. The neoplasia-specificity of ϩ7 has been questioned, however, both in the context of colorectal carcinogenesis and in general.…”

Section: Discussionmentioning

confidence: 99%

“…5-7,16 -18 Similar results have been obtained by CGH analyses of colorectal adenomas and carcinomas. 11,25,26 In adenomas, Ried et al 12 described gain of chromosome 13 material in 1 of 26 adenomas and gain of chromosome 20 material in 3 of 26 adenomas. All cases with these changes were described as high-grade adenomas.…”

Section: Discussionmentioning

confidence: 99%

Assessments of clonal composition of colorectal adenomas by FISH analysis of chromosomes 1, 7, 13 and 20

et al. 2001

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Chromosome banding analysis has shown that numerical aberrations, in particular gains of chromosomes 7, 13 and 20, are common in colorectal adenomas but cannot provide reliable information on the size of the abnormal clones in vivo. We examined interphase nuclei from 70 colorectal adenomas, of which 64 had been previously karyotyped, using fluorescence in situ hybridization (FISH) with probes for the pericentromeric regions of chromosomes 1, 7, 13 and 20. Gain of chromosome 7 was seen in 34% of the analyzed adenomas, ؉13 was seen in 44% and trisomy 20 was found in 32% of the adenomas, verifying that the trisomies are in vivo phenomena. The median proportion of cells with trisomy was larger than 50%. A comparison with the G-banding analysis showed a good correlation between the results yielded by the 2 methods. Based on the clonal size and karyotypic findings, a likely order of events during clonal evolution could be ascribed to each case. More than 1 numerical aberration was detected by FISH analysis in 16 adenomas. In 6 adenomas, a clone with only trisomy 7 was present alongside a clone with additional gain(s) of chromosomes 13 and/or 20. Seven cases had gain of chromosome 13 and/or gain of chromosome 20 in the largest clone, suggesting that a clone with either of these changes was present before the changes in chromosome 7 copy number took place. On the basis of the results of this combined meta-and interphase cytogenetic study, we conclude that gains of chromosomes 7, 13 and 20 are common in colorectal adenomas and that the trisomies usually are present in a large proportion of the cells. They seem to be primary chromosome aberrations in some adenomas, whereas in others they arise secondarily as part of the clonal evolution. Although the first gain usually is of chromosome 7, it is evident that it is the end result of the chromosomal aberrations, not the exact sequence in which they occur, that determines the pathogenetic consequences. Tumor progression is generally considered to be a multistep process characterized by the accumulation of genetic aberrations. 1 In the large bowel, early premalignant stages of tumorigenesis as well as later, malignant lesions are readily identified phenotypically as adenomas and adenocarcinomas. The acquired genetic aberrations characteristic of these 2 tumor types have been extensively examined at both the molecular genetic and cytogenetic level. The nonrandom changes thus revealed include, in carcinomas, structural rearrangements of chromosomes 1, 8, 13 and 17 and the numerical changes ϩ7, ϩ13, Ϫ17, Ϫ18, ϩ20, ϪY 1,2 and, in adenomas, gain of chromosomes 7, 13 and 20, loss of chromosome 18, as well as the structural rearrangements del(1p) and, less frequently, del(8p), i(13q), and del(17p). 2,3 Although no single cytogenetic aberration can be said to distinguish large bowel adenomas from carcinomas with absolute certainty, the former tumors generally have simpler karyotypes than do the malignant ones.The information value of the cytogenetic analysis of colorectal adenomas, as...

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Comparative Genome Hybridization

Chen

Korenberg

2002

Wiley Encyclopedia of Molecular Medicine

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Chromosomal gains and losses in primary colorectal carcinomas detected by CGH and their associations with tumour DNA ploidy, genotypes and phenotypes

Cited by 140 publications

References 53 publications

Genetic profiling of stage I and II colorectal cancer may predict metastatic relapse

Genetic profiling of stage I and II colorectal cancer may predict metastatic relapse

Assessments of clonal composition of colorectal adenomas by FISH analysis of chromosomes 1, 7, 13 and 20

Comparative Genome Hybridization

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