Chromosomal imbalances in the colorectal carcinomas with microsatellite instability

Long Shan Li, Nam Gyun Kim, Se Hoon Kim, Chanil Park, Hyunki Kim, Hyun Ju Kang, Kwi Hye Koh, Soo Nyung Kim, Won Ho Kim, Nam Kyu Kim, Hoguen Kim

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Abstract

Recent molecular genetic studies have revealed that two major types of genomic instabilities, chromosomal instability and microsatellite instability, exist in the colorectal carcinomas. To clarify the relationship between chromosomal abnormalities and mismatch repair gene defects in colorectal carcinomas, we performed a chromosomal analysis on 39 colorectal carcinomas with high-microsatellite instability (MSI-H) and compared the results obtained with those of 20 right-sided microsatellite-stable (MSS) colorectal carcinomas. Chromosomal imbalances (CIs) in MSS colorectal carcinomas were more frequent than in MSI-H colon carcinomas by comparative genomic hybridization analysis (70% versus 31%, P = 0.004). The CI patterns of MSI-H and MSS carcinomas were different. Frequent CIs in MSI-H colon carcinomas were gains of 4q (15%) and 8q (8%), and losses of 9q (21%), 1p (18%), and 11q (18%). In contrast, frequent CIs in right-sided MSS colon carcinomas were gains of 8q (50%), 13q (35%), and 20q (25%), and losses of 18q (55%), 15q (35%), and 17p (30%). We compared the mutation status of 45 target genes and CIs in our MSI-H tumors. Among these 45 target genes, mutation of hRAD50, a member of the DNA repair genes, and FLJ11383 were significantly related to MSI-H colorectal carcinomas with CIs (P = 0.01 and P = 0.02, respectively). Our findings indicate that unique CIs were present in a subset of MSI-H colorectal carcinomas and that these CIs are related to the mutation of several target genes, especially of hRAD50.

Original languageEnglish
Pages (from-to)1429-1436
Number of pages8
JournalAmerican Journal of Pathology
Volume163
Issue number4
DOIs
Publication statusPublished - 2003 Oct 1

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

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    Li, L. S., Kim, N. G., Kim, S. H., Park, C., Kim, H., Kang, H. J., Koh, K. H., Kim, S. N., Kim, W. H., Kim, N. K., & Kim, H. (2003). Chromosomal imbalances in the colorectal carcinomas with microsatellite instability. American Journal of Pathology, 163(4), 1429-1436. https://doi.org/10.1016/S0002-9440(10)63500-6