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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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Gains of 5p and 12p in carcinomatoses. Gains of 5p (samples 17C, 64C1, and 64C2) and 12p (samples 36C, 64C1, and 62C2) were clearly detected by CGH. The central line (red) in the CGH profile shows the average fluorescence ratio along the chromosome, and the flanking curves (brown) represent the 95% confidence interval. The red and the green lines represent the cut-off values, 0.83 and 1.17, respectively.
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Figure 4: Gains of 5p and 12p in carcinomatoses. Gains of 5p (samples 17C, 64C1, and 64C2) and 12p (samples 36C, 64C1, and 62C2) were clearly detected by CGH. The central line (red) in the CGH profile shows the average fluorescence ratio along the chromosome, and the flanking curves (brown) represent the 95% confidence interval. The red and the green lines represent the cut-off values, 0.83 and 1.17, respectively.

Mentions: Peritoneal carcinomatosis reflects the regional spread of cancer cells within the peritoneal cavity. Although carcinomatosis is not always associated with widespread visceral or extra-peritoneal disease, it almost always reflects an incurable disease [31,32]. The present comparisons of the distribution and frequency of specific chromosomal imbalances among the different tumor stages revealed significant differences between carcinomatoses and each of the other stages of the disease regarding gains at 5p and 12p (Table 1). The frequencies of 5p gains were not significantly different between primary carcinomas and carcinomatoses (Table 1), is best explained by small sample sets. However, these chromosome aberrations are indeed quite rare in primary colorectal carcinomas as evaluated from previous studies, and among 670 cases the average frequencies for 5p and 12p gains were less than 10% each [11-23,28,33-40]. Summarized, the present study and the previous data, lead us to speculate that genes located at these chromosome arms are involved in development of peritoneal carcinomatoses. Although gain of 5p12-p14 was confirmed in both samples from the same patient (Fig. 4), a smallest region of overlapping gain can not determined from one case only.


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)

Gains of 5p and 12p in carcinomatoses. Gains of 5p (samples 17C, 64C1, and 64C2) and 12p (samples 36C, 64C1, and 62C2) were clearly detected by CGH. The central line (red) in the CGH profile shows the average fluorescence ratio along the chromosome, and the flanking curves (brown) represent the 95% confidence interval. The red and the green lines represent the cut-off values, 0.83 and 1.17, respectively.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 4: Gains of 5p and 12p in carcinomatoses. Gains of 5p (samples 17C, 64C1, and 64C2) and 12p (samples 36C, 64C1, and 62C2) were clearly detected by CGH. The central line (red) in the CGH profile shows the average fluorescence ratio along the chromosome, and the flanking curves (brown) represent the 95% confidence interval. The red and the green lines represent the cut-off values, 0.83 and 1.17, respectively.
Mentions: Peritoneal carcinomatosis reflects the regional spread of cancer cells within the peritoneal cavity. Although carcinomatosis is not always associated with widespread visceral or extra-peritoneal disease, it almost always reflects an incurable disease [31,32]. The present comparisons of the distribution and frequency of specific chromosomal imbalances among the different tumor stages revealed significant differences between carcinomatoses and each of the other stages of the disease regarding gains at 5p and 12p (Table 1). The frequencies of 5p gains were not significantly different between primary carcinomas and carcinomatoses (Table 1), is best explained by small sample sets. However, these chromosome aberrations are indeed quite rare in primary colorectal carcinomas as evaluated from previous studies, and among 670 cases the average frequencies for 5p and 12p gains were less than 10% each [11-23,28,33-40]. Summarized, the present study and the previous data, lead us to speculate that genes located at these chromosome arms are involved in development of peritoneal carcinomatoses. Although gain of 5p12-p14 was confirmed in both samples from the same patient (Fig. 4), a smallest region of overlapping gain can not determined from one case only.

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