Comparative genomic hybridization analysis of primary colorectal carcinomas and their synchronous metastases

Al-Mulla, Fahd; Keith, W. Nicol; Pickford, I. R.; Going, James J.; Birnie, G.D.

doi:10.1002/(sici)1098-2264(199904)24:4<306::aid-gcc3>3.0.co;2-5

Cited by 119 publications

(88 citation statements)

References 22 publications

(14 reference statements)

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“…11,12 These results supported ours; above all, we emphasize that some important genes appear to be contained in 20q and to play an important role in liver metastases. Furthermore, we examined the follow-up surveys of all cases and compared cases with and without loss at 18q and with gains at 8q and 20q to determine the usefulness of these genetic alterations as prognostic markers.…”

supporting

confidence: 88%

Chromosomal aberrations in colorectal cancers and liver metastases analyzed by comparative genomic hybridization

et al. 2001

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Comparative genomic hybridization (CGH) was used to screen for changes in the number of DNA sequence copies in 30 primary colorectal cancers and 16 liver metastases, to identify regions that contain genes important for the development and progression of colorectal cancer. In primary colorectal cancer, we found frequent gains at 7p21 (36.7%), 7q31-36 (30%), 8q23-24 (43.0%), 12p (30%) Many detailed reports have been published on the carcinogenesis of colorectal cancer. Several genetic aberrations are required for tumor initiation and progression. 1 These aberrations include activation of the SRC and RAS oncogenes 2,3 along with inactivation of the FAP 4,5 and DCC 6 tumor suppressors and loss of TP53 function. 7 However, genetic changes involved in the progression and metastases of colorectal cancer remain unclear. To investigate differences in chromosomal aberrations between primary colorectal cancer and metastatic liver tumor, we used comparative genomic hybridization (CGH). CGH is based on dual-color fluorescence in situ hybridization (FISH) using differentially labeled tumors and reference DNA as a probe. 8,9 The efficacy of CGH is based on the concept that regions with an increase in the number of copies reveal sites that may contain dominantly acting oncogenes, whereas regions with a reduction may harbor putative tumorsuppressor genes. 8 Our aim was to generate a comprehensive picture of genomic and chromosomal aberrations that occur during the development of metastases of colorectal cancers and to identify those chromosomal regions that contain genes important for the development and progression of colorectal cancer.,Colorectal adenoma and adenocarcinoma have previously been analyzed by CGH, 10 as have primary and metastatic liver tumors. 11,12 These results supported ours; above all, we emphasize that some important genes appear to be contained in 20q and to play an important role in liver metastases. Furthermore, we examined the follow-up surveys of all cases and compared cases with and without loss at 18q and with gains at 8q and 20q to determine the usefulness of these genetic alterations as prognostic markers. MATERIAL AND METHODS Samples and DNA preparationPrimary tumors and metastatic liver tumors from 44 cancer patients with colorectal cancer (Table I) were classified according to the UICC system. These samples were provided by the Department of Digestive Surgery, Kyoto Prefectural University of Medicine (Kyoto, Japan). After surgical resection, tissues were frozen and stored at -80°C and DNA was extracted. CGHCGH was performed as described previously. 13 In brief, tumor DNA was labeled with FITC-dUTP and controlled DNA and extracted from a normal male with the aid of Texas red-dUTP using nick translation. Metaphase spreads were denatured at 75°C for 2.1 min in a formamide solution [70% formamide, 2 ϫ SCC (pH 7.0)] and dehydrated in an ethanol series of 70%, 85% and 100%. Labeled tumor and normal DNAs together with 10 g unlabeled cot-1 DNA was mixed with 50% formamide, 10% dextran sulfate and 2 ϫ SSC...

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supporting

confidence: 88%

Chromosomal aberrations in colorectal cancers and liver metastases analyzed by comparative genomic hybridization

et al. 2001

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“…Korn and colleagues 186 found no consistent difference between primary tumours and synchronous liver metastases, whereas Al-Mulla et al 187 found, in all cases studied, that liver or lymph node metastases had acquired new genetic alterations not present in the primary lesion. In addition, this latter group showed that loss of 17p was signi®cantly associated with Dukes' stage C and lymph node metastases, while gain of chromosomal arms 6p and 17q was associated with Dukes' stage`D' and liver metastases.…”

Section: Molecular Cytogenetic Evidencementioning

confidence: 86%

The colorectal adenoma–carcinoma sequence

Leslie

Carey

Pratt

et al. 2002

British Journal of Surgery

584

448

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Background: It is widely accepted that the adenoma±carcinoma sequence represents the process by which most, if not all, colorectal cancers arise. The evidence supporting this hypothesis has increased rapidly in recent years and the purpose of this article is to review this evidence critically and highlight its clinical signi®cance.Methods: Medline searches were used to identify recent key articles relating to the adenoma±carcinoma sequence. Further pertinent articles were obtained by manual scanning of the reference lists of identi®ed papers.Results: The evidence supporting the adenoma±carcinoma sequence can be classi®ed as epidemiological, clinicopathological and genetic. The most recent and largest body of data relates to molecular genetic events and their cellular effects; however, many other approaches, such as cytogenetics, molecular cytogenetics and cytometry, have also yielded valuable information.Conclusion: Recent work continues to support the adenoma±carcinoma sequence, but there is a paucity of data on the interrelationship between different genetic mutations and on the relationship between molecular and other types of genetic abnormalities. The clinical utility of the observations described has yet to be fully realized and global genetic analysis of colorectal tumours may prove to be central in rational adenoma management. IntroductionColorectal cancer is the second leading cause of cancerrelated death in the Western world; in the UK there are currently around 30 000 new cases per annum and 17 000 related deaths 1 . In recent years our understanding of the cellular and molecular events underlying the development of colorectal cancer has improved immeasurably but, despite this and advances in surgery, radiotherapy and chemotherapy, the average 5-year survival rate remains around 40 per cent 1 . One of the most important fundamental concepts in colorectal cancer to emerge in recent years has been the adenoma±carcinoma sequence, a term that describes the stepwise progression from normal to dysplastic epithelium to carcinoma associated with the accumulation of multiple clonally selected genetic alterations. This concept not only provides an excellent model to study the genesis of invasive cancer, but also affords a means of preventing colorectal cancer by endoscopic removal of precursor lesions.The appropriate management of individuals with precursor adenomatous polyps (adenomas) is of the utmost importance. It is known that after removal of such polyps 30±35 per cent of patients will have further adenomas detected at 3±4 years 2±4 and this has led to a policy of endoscopic surveillance for all adenoma-bearers 5 . However, given that approximately 40 per cent of the Western population will develop adenomas 6±8 and only 3 per cent will go on to suffer from colorectal cancer, it is clear that only a small proportion of adenomas progress to malignancy. Unfortunately, there are no reliable criteria available that can predict adenoma progression or recurrence, and the important questions of which individuals...

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“…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%

“…After applying the probe, slides were incubated at 371C in a humid environment for 72 h. The slides were finally washed with 70% formamide in 2 Â SSC buffers and stained with fluorescent antibodies and DAPI as described previously. 10 Images were captured by CCD camera (JVL, Japan) and then analysed by ISIS s software (Metasystems, GmbH). Typically, 10-20 metaphases were captured using the appropriate filters.…”

Section: Metaphase Cghmentioning

confidence: 99%

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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Comparative genomic hybridization analysis of primary colorectal carcinomas and their synchronous metastases

Cited by 119 publications

References 22 publications

Chromosomal aberrations in colorectal cancers and liver metastases analyzed by comparative genomic hybridization

Chromosomal aberrations in colorectal cancers and liver metastases analyzed by comparative genomic hybridization

The colorectal adenoma–carcinoma sequence

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

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