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Genome characteristics of primary carcinomas, local recurrences, carcinomatoses, and liver metastases from colorectal cancer patients.

Diep CB, Teixeira MR, Thorstensen L, Wiig JN, Eknaes M, Nesland JM, Giercksky KE, Johansson B, Lothe RA - Mol. Cancer (2004)

Bottom Line: Several genetic imbalances, such as gains of 7, 8q, 13q, and 20, and losses of 4q, 8p, 17p, and 18, were common in all groups.In contrast, gains of 5p and 12p were more common in the carcinomatoses than in other stages of the disease.This is the first genome profiling of local recurrences and carcinomatoses, and gains of 5p and 12p seem to be particularly important for the spread of the CRC cells within the peritoneal cavity.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, N-0310 Oslo, Norway. chieud@radium.uio.no

ABSTRACT

Background: Colorectal cancer (CRC) is one of the most common causes of cancer-related deaths in the Western world, and despite the fact that metastases are usually the ultimate cause of deaths, the knowledge of the genetics of advanced stages of this disease is limited. In order to identify potential genetic abnormalities underlying the development of local and distant metastases in CRC patients, we have, by comparative genomic hybridization, compared the DNA copy number profiles of 10 primary carcinomas, 14 local recurrences, 7 peritoneal carcinomatoses, and 42 liver metastases from 61 CRC patients.

Results: The median number of aberrations among the primary carcinomas, local recurrences, carcinomatoses, and liver metastases was 10, 6, 13, and 14, respectively. Several genetic imbalances, such as gains of 7, 8q, 13q, and 20, and losses of 4q, 8p, 17p, and 18, were common in all groups. In contrast, gains of 5p and 12p were more common in the carcinomatoses than in other stages of the disease. With hierarchical cluster analysis, liver metastases could be divided into two main subgroups according to clusters of chromosome changes.

Conclusions: Each stage of CRC progression is characterized by a particular genetic profile, and both carcinomatoses and liver metastases are more genetically complex than local recurrences and primary carcinomas. This is the first genome profiling of local recurrences and carcinomatoses, and gains of 5p and 12p seem to be particularly important for the spread of the CRC cells within the peritoneal cavity.

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Hierarchical clustering of liver metastases from colorectal cancer patients. The hierarchical clustering is based on chromosome aberrations of all chromosome arms. Chromosome arms 13p, 14p, 15p, 21p, 22p, and chromosome Y, due to high content of heterochromatin, were excluded from the cluster analysis. The chromosome arms are given in the right dendogram (gains in green and losses in blue). Each tumor sample is depicted at the top of the dendogram. Each row represents alterations from a separate chromosome arm over all tumor samples, and each column represents all changes in each tumor.
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Figure 3: Hierarchical clustering of liver metastases from colorectal cancer patients. The hierarchical clustering is based on chromosome aberrations of all chromosome arms. Chromosome arms 13p, 14p, 15p, 21p, 22p, and chromosome Y, due to high content of heterochromatin, were excluded from the cluster analysis. The chromosome arms are given in the right dendogram (gains in green and losses in blue). Each tumor sample is depicted at the top of the dendogram. Each row represents alterations from a separate chromosome arm over all tumor samples, and each column represents all changes in each tumor.

Mentions: A hierarchical cluster analysis was performed for the colorectal tumors based on the gains and losses from all chromosome arms (Fig. 2). No chromosome changes seemed to be tumor-stage specific. Furthermore, a separate cluster analysis for the 37 liver metastases is illustrated in Fig. 3. The majority of the liver metastases harbored changes at 7, 8p, 13q, 17p, 18, and 20 (pink tree). The top dendogram indicates that the liver metastases can be subdivided into two main groups (red and brown trees) according to the chromosome changes, one of these subgroup is characterized by additional changes at 4q, 5q, 6p, 8q, 16 (blue tree).


Genome characteristics of primary carcinomas, local recurrences, carcinomatoses, and liver metastases from colorectal cancer patients.

Diep CB, Teixeira MR, Thorstensen L, Wiig JN, Eknaes M, Nesland JM, Giercksky KE, Johansson B, Lothe RA - Mol. Cancer (2004)

Hierarchical clustering of liver metastases from colorectal cancer patients. The hierarchical clustering is based on chromosome aberrations of all chromosome arms. Chromosome arms 13p, 14p, 15p, 21p, 22p, and chromosome Y, due to high content of heterochromatin, were excluded from the cluster analysis. The chromosome arms are given in the right dendogram (gains in green and losses in blue). Each tumor sample is depicted at the top of the dendogram. Each row represents alterations from a separate chromosome arm over all tumor samples, and each column represents all changes in each tumor.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC373453&req=5

Figure 3: Hierarchical clustering of liver metastases from colorectal cancer patients. The hierarchical clustering is based on chromosome aberrations of all chromosome arms. Chromosome arms 13p, 14p, 15p, 21p, 22p, and chromosome Y, due to high content of heterochromatin, were excluded from the cluster analysis. The chromosome arms are given in the right dendogram (gains in green and losses in blue). Each tumor sample is depicted at the top of the dendogram. Each row represents alterations from a separate chromosome arm over all tumor samples, and each column represents all changes in each tumor.
Mentions: A hierarchical cluster analysis was performed for the colorectal tumors based on the gains and losses from all chromosome arms (Fig. 2). No chromosome changes seemed to be tumor-stage specific. Furthermore, a separate cluster analysis for the 37 liver metastases is illustrated in Fig. 3. The majority of the liver metastases harbored changes at 7, 8p, 13q, 17p, 18, and 20 (pink tree). The top dendogram indicates that the liver metastases can be subdivided into two main groups (red and brown trees) according to the chromosome changes, one of these subgroup is characterized by additional changes at 4q, 5q, 6p, 8q, 16 (blue tree).

Bottom Line: Several genetic imbalances, such as gains of 7, 8q, 13q, and 20, and losses of 4q, 8p, 17p, and 18, were common in all groups.In contrast, gains of 5p and 12p were more common in the carcinomatoses than in other stages of the disease.This is the first genome profiling of local recurrences and carcinomatoses, and gains of 5p and 12p seem to be particularly important for the spread of the CRC cells within the peritoneal cavity.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, N-0310 Oslo, Norway. chieud@radium.uio.no

ABSTRACT

Background: Colorectal cancer (CRC) is one of the most common causes of cancer-related deaths in the Western world, and despite the fact that metastases are usually the ultimate cause of deaths, the knowledge of the genetics of advanced stages of this disease is limited. In order to identify potential genetic abnormalities underlying the development of local and distant metastases in CRC patients, we have, by comparative genomic hybridization, compared the DNA copy number profiles of 10 primary carcinomas, 14 local recurrences, 7 peritoneal carcinomatoses, and 42 liver metastases from 61 CRC patients.

Results: The median number of aberrations among the primary carcinomas, local recurrences, carcinomatoses, and liver metastases was 10, 6, 13, and 14, respectively. Several genetic imbalances, such as gains of 7, 8q, 13q, and 20, and losses of 4q, 8p, 17p, and 18, were common in all groups. In contrast, gains of 5p and 12p were more common in the carcinomatoses than in other stages of the disease. With hierarchical cluster analysis, liver metastases could be divided into two main subgroups according to clusters of chromosome changes.

Conclusions: Each stage of CRC progression is characterized by a particular genetic profile, and both carcinomatoses and liver metastases are more genetically complex than local recurrences and primary carcinomas. This is the first genome profiling of local recurrences and carcinomatoses, and gains of 5p and 12p seem to be particularly important for the spread of the CRC cells within the peritoneal cavity.

Show MeSH
Related in: MedlinePlus