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Characterization of sporadic colon cancer by patterns of genomic instability.

Publication ,  Journal Article
Goel, A; Arnold, CN; Niedzwiecki, D; Chang, DK; Ricciardiello, L; Carethers, JM; Dowell, JM; Wasserman, L; Compton, C; Mayer, RJ; Boland, CR ...
Published in: Cancer Res
April 1, 2003

Colorectal cancer (CRC) can progress through two pathways of genomic instability: chromosomal (CIN) and microsatellite instability (MSI). We hypothesized that these two pathways are not always independent and that some tumors therefore show a significant degree of overlap between these two mechanisms. We classified 209 high-risk stage II and stage III sporadic CRCs based on their MSI status, using a National Cancer Institute-recommended panel of microsatellite markers, and also identified MSI-associated mutations of CRC target genes such as TGFbetaRII. Evidence for CIN was gathered by identifying loss of heterozygosity (LOH) events on chromosomal arms 1p, 2p, 3p, 5q, 17p, and 18q, which are regions harboring mismatch-repair and tumor-suppressor genes that are significant in CRC development. Results of all molecular markers tested were correlated with clinicopathological variables of the cohort, including treatment outcome. Of the 209 cases, 65% cancers were microsatellite stable, 21% were MSI-low, and 14% were MSI-high (MSI-H). Overall, 51% of the tumors had at least one LOH event, with most frequent chromosomal losses observed on 18q (72.5%), followed by 5q (22%), 17p (21%), and 3p (14%). Interestingly, we observed a significant degree of overlap between MSI and CIN pathways. Of 107 cancers with LOH events, 7 (6.5%) were also MSI-H, and of 30 cancers that were MSI-H, 7 (23.3%) also had one or more LOH events. We also found that 37.8% of microsatellite-stable cancers had no LOH events identified, thus comprising a subgroup of tumors that were not representative of either of these two pathways of genomic instability. Our data suggest that molecular mechanisms of genomic instability are not necessarily independent and may not be fully defined by either the MSI or CIN pathways.

Duke Scholars

Published In

Cancer Res

ISSN

0008-5472

Publication Date

April 1, 2003

Volume

63

Issue

7

Start / End Page

1608 / 1614

Location

United States

Related Subject Headings

  • Oncology & Carcinogenesis
  • Neoplasm Staging
  • Mutation
  • Middle Aged
  • Microsatellite Repeats
  • Male
  • Loss of Heterozygosity
  • Humans
  • Female
  • Colorectal Neoplasms
 

Citation

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Goel, A., Arnold, C. N., Niedzwiecki, D., Chang, D. K., Ricciardiello, L., Carethers, J. M., … Boland, C. R. (2003). Characterization of sporadic colon cancer by patterns of genomic instability. Cancer Res, 63(7), 1608–1614.
Goel, Ajay, Christian N. Arnold, Donna Niedzwiecki, Dong K. Chang, Luigi Ricciardiello, John M. Carethers, Jeannette M. Dowell, et al. “Characterization of sporadic colon cancer by patterns of genomic instability.Cancer Res 63, no. 7 (April 1, 2003): 1608–14.
Goel A, Arnold CN, Niedzwiecki D, Chang DK, Ricciardiello L, Carethers JM, et al. Characterization of sporadic colon cancer by patterns of genomic instability. Cancer Res. 2003 Apr 1;63(7):1608–14.
Goel, Ajay, et al. “Characterization of sporadic colon cancer by patterns of genomic instability.Cancer Res, vol. 63, no. 7, Apr. 2003, pp. 1608–14.
Goel A, Arnold CN, Niedzwiecki D, Chang DK, Ricciardiello L, Carethers JM, Dowell JM, Wasserman L, Compton C, Mayer RJ, Bertagnolli MM, Boland CR. Characterization of sporadic colon cancer by patterns of genomic instability. Cancer Res. 2003 Apr 1;63(7):1608–1614.

Published In

Cancer Res

ISSN

0008-5472

Publication Date

April 1, 2003

Volume

63

Issue

7

Start / End Page

1608 / 1614

Location

United States

Related Subject Headings

  • Oncology & Carcinogenesis
  • Neoplasm Staging
  • Mutation
  • Middle Aged
  • Microsatellite Repeats
  • Male
  • Loss of Heterozygosity
  • Humans
  • Female
  • Colorectal Neoplasms