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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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Graphic comparison of the overall genomic gains (A) and losses (B) detected by CGH in different CRC stages. For each case, the presence or absence of imbalance in every chromosome band (from 1p36 to Xq28) was computed in a spreadsheet. The total number of imbalances detected in every band was then used to prepare the graphic comparison. All chromosome arms were involved in imbalances. (A) Loss of 18q was one of the most frequent aberrations seen in all groups. In addition to 18q loss, primary carcinomas and liver metastases often showed loss of 8p. Additionally, liver metastases and carcinomatoses frequently harbored loss of 4q. (B) Gain of 8q and 20q were common in all tumor types. In addition, carcinomatoses often contained gains of 5p, 7p, 9q, 12, and 13q, whereas liver metastases often showed gains of 7p, and 13q. * Multiple samples from a single tumor (case no. 53R1 and 53R2; 64C1 and 64C2; 21L1 and 21L2; 42L1 and 42L2; 52L1 and 52L2; 76L1, 76L2, and 76L3) were counted as one sample.
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Figure 1: Graphic comparison of the overall genomic gains (A) and losses (B) detected by CGH in different CRC stages. For each case, the presence or absence of imbalance in every chromosome band (from 1p36 to Xq28) was computed in a spreadsheet. The total number of imbalances detected in every band was then used to prepare the graphic comparison. All chromosome arms were involved in imbalances. (A) Loss of 18q was one of the most frequent aberrations seen in all groups. In addition to 18q loss, primary carcinomas and liver metastases often showed loss of 8p. Additionally, liver metastases and carcinomatoses frequently harbored loss of 4q. (B) Gain of 8q and 20q were common in all tumor types. In addition, carcinomatoses often contained gains of 5p, 7p, 9q, 12, and 13q, whereas liver metastases often showed gains of 7p, and 13q. * Multiple samples from a single tumor (case no. 53R1 and 53R2; 64C1 and 64C2; 21L1 and 21L2; 42L1 and 42L2; 52L1 and 52L2; 76L1, 76L2, and 76L3) were counted as one sample.

Mentions: The complete CGH profiles are presented in the supplementary Table 1 (additional data file 1). All tumors, except one primary carcinoma, three local recurrences and one liver metastasis, exhibited DNA copy number changes, and the overall copy number profiles for each tumor stage are illustrated in Fig. 1. The number of imbalances per case ranged from 0 to 28 (median, 11). Although all chromosomes were involved, the distribution of the imbalances was clearly nonrandom. The most common copy number changes, found in more than 20% of each tumor group, were gains of 7, 8q, 13q, and 20, and losses of 4q, 8p, 17p, and 18, but however, frequency variations were observed among primary tumors, local recurrences, and liver metastases (Fig. 1). Twenty tumors showed amplifications (Table 1, supplementary data, additional data file 1) in one to nine discrete regions: chromosome arms 13q (ten cases), 20q (nine cases), 8q (eight cases), 20p (six cases), 5p (one case), and chromosome X (two cases) and 7 (one case). The frequency of amplification did not differ significantly among the different tumor groups.


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)

Graphic comparison of the overall genomic gains (A) and losses (B) detected by CGH in different CRC stages. For each case, the presence or absence of imbalance in every chromosome band (from 1p36 to Xq28) was computed in a spreadsheet. The total number of imbalances detected in every band was then used to prepare the graphic comparison. All chromosome arms were involved in imbalances. (A) Loss of 18q was one of the most frequent aberrations seen in all groups. In addition to 18q loss, primary carcinomas and liver metastases often showed loss of 8p. Additionally, liver metastases and carcinomatoses frequently harbored loss of 4q. (B) Gain of 8q and 20q were common in all tumor types. In addition, carcinomatoses often contained gains of 5p, 7p, 9q, 12, and 13q, whereas liver metastases often showed gains of 7p, and 13q. * Multiple samples from a single tumor (case no. 53R1 and 53R2; 64C1 and 64C2; 21L1 and 21L2; 42L1 and 42L2; 52L1 and 52L2; 76L1, 76L2, and 76L3) were counted as one sample.
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Related In: Results  -  Collection

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Figure 1: Graphic comparison of the overall genomic gains (A) and losses (B) detected by CGH in different CRC stages. For each case, the presence or absence of imbalance in every chromosome band (from 1p36 to Xq28) was computed in a spreadsheet. The total number of imbalances detected in every band was then used to prepare the graphic comparison. All chromosome arms were involved in imbalances. (A) Loss of 18q was one of the most frequent aberrations seen in all groups. In addition to 18q loss, primary carcinomas and liver metastases often showed loss of 8p. Additionally, liver metastases and carcinomatoses frequently harbored loss of 4q. (B) Gain of 8q and 20q were common in all tumor types. In addition, carcinomatoses often contained gains of 5p, 7p, 9q, 12, and 13q, whereas liver metastases often showed gains of 7p, and 13q. * Multiple samples from a single tumor (case no. 53R1 and 53R2; 64C1 and 64C2; 21L1 and 21L2; 42L1 and 42L2; 52L1 and 52L2; 76L1, 76L2, and 76L3) were counted as one sample.
Mentions: The complete CGH profiles are presented in the supplementary Table 1 (additional data file 1). All tumors, except one primary carcinoma, three local recurrences and one liver metastasis, exhibited DNA copy number changes, and the overall copy number profiles for each tumor stage are illustrated in Fig. 1. The number of imbalances per case ranged from 0 to 28 (median, 11). Although all chromosomes were involved, the distribution of the imbalances was clearly nonrandom. The most common copy number changes, found in more than 20% of each tumor group, were gains of 7, 8q, 13q, and 20, and losses of 4q, 8p, 17p, and 18, but however, frequency variations were observed among primary tumors, local recurrences, and liver metastases (Fig. 1). Twenty tumors showed amplifications (Table 1, supplementary data, additional data file 1) in one to nine discrete regions: chromosome arms 13q (ten cases), 20q (nine cases), 8q (eight cases), 20p (six cases), 5p (one case), and chromosome X (two cases) and 7 (one case). The frequency of amplification did not differ significantly among the different tumor groups.

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