Chromosomal instability in microsatellite-unstable and stable colon cancer

Karolin Trautmann, Jonathan P. Terdiman, Amy J. French, Ritu Roydasgupta, Nancy Sein, Sanjay Kakar, Jane Fridlyand, Antoine M. Snijders, Donna Albertson, Stephen N. Thibodeau, Frederic M. Waldman

Research output: Contribution to journalArticle

Abstract

Purpose: The genomic instability in colon cancer can be divided into at least two major types, microsatellite instability (MSI) or chromosomal instability (CIN). Although initially felt to be mutually exclusive, recent evidence suggests that there may be overlap between the two. The aim of this study was to identify chromosomal alterations at high resolution in sporadic colon cancers with high-level microsatellite instability (MSI-H) and to compare them to those present in a set of matched microsatellite stable (MSS) tumors. Experimental Design: Array-based comparative genomic hybridization was used to analyze a set of 23 sporadic MSI-H and 23 MSS colon cancers matched for location, gender, stage, and age. The arrays consisted of 2,464 bacterial artificial chromosome clones. Results: MSI and MSS colon cancers differed significantly with respect to frequency and type of chromosomal alterations. The median fraction of genome altered was lower among MSI-H tumors than MSS tumors (2.8% versus 30.7%, P = 0.00006). However, the MSI-H tumors displayed a range of genomic alterations, from the absence of detectable alterations to extensive alterations. Frequent alterations in MSI-H tumors included gains of chromosomes 8, 12, and 13, and loss of 15q14. In contrast, the most frequent alterations in MSS tumors were gains of 7, 13, 8q, and 20, and losses of 8p, 17p, and 18. A small, previously uncharacterized, genomic deletion on 16p13.2, found in 35% of MSI-H and 21% of MSS tumors, was confirmed by fluorescence in situ hybridization. Conclusion: MSI and CIN are not mutually exclusive forms of genomic instability in sporadic colon cancer, with MSI tumors also showing varying degrees of CIN.

Original languageEnglish (US)
Pages (from-to)6379-6385
Number of pages7
JournalClinical Cancer Research
Volume12
Issue number21
DOIs
StatePublished - Nov 1 2006

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Chromosomal Instability
Microsatellite Instability
Microsatellite Repeats
Colonic Neoplasms
Neoplasms
Genomic Instability
Bacterial Artificial Chromosomes
Chromosomes, Human, Pair 13
Chromosomes, Human, Pair 12
Chromosomes, Human, Pair 8
Comparative Genomic Hybridization
Fluorescence In Situ Hybridization
Research Design
Clone Cells
Genome

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Trautmann, K., Terdiman, J. P., French, A. J., Roydasgupta, R., Sein, N., Kakar, S., ... Waldman, F. M. (2006). Chromosomal instability in microsatellite-unstable and stable colon cancer. Clinical Cancer Research, 12(21), 6379-6385. https://doi.org/10.1158/1078-0432.CCR-06-1248

Chromosomal instability in microsatellite-unstable and stable colon cancer. / Trautmann, Karolin; Terdiman, Jonathan P.; French, Amy J.; Roydasgupta, Ritu; Sein, Nancy; Kakar, Sanjay; Fridlyand, Jane; Snijders, Antoine M.; Albertson, Donna; Thibodeau, Stephen N.; Waldman, Frederic M.

In: Clinical Cancer Research, Vol. 12, No. 21, 01.11.2006, p. 6379-6385.

Research output: Contribution to journalArticle

Trautmann, K, Terdiman, JP, French, AJ, Roydasgupta, R, Sein, N, Kakar, S, Fridlyand, J, Snijders, AM, Albertson, D, Thibodeau, SN & Waldman, FM 2006, 'Chromosomal instability in microsatellite-unstable and stable colon cancer', Clinical Cancer Research, vol. 12, no. 21, pp. 6379-6385. https://doi.org/10.1158/1078-0432.CCR-06-1248
Trautmann K, Terdiman JP, French AJ, Roydasgupta R, Sein N, Kakar S et al. Chromosomal instability in microsatellite-unstable and stable colon cancer. Clinical Cancer Research. 2006 Nov 1;12(21):6379-6385. https://doi.org/10.1158/1078-0432.CCR-06-1248
Trautmann, Karolin ; Terdiman, Jonathan P. ; French, Amy J. ; Roydasgupta, Ritu ; Sein, Nancy ; Kakar, Sanjay ; Fridlyand, Jane ; Snijders, Antoine M. ; Albertson, Donna ; Thibodeau, Stephen N. ; Waldman, Frederic M. / Chromosomal instability in microsatellite-unstable and stable colon cancer. In: Clinical Cancer Research. 2006 ; Vol. 12, No. 21. pp. 6379-6385.
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abstract = "Purpose: The genomic instability in colon cancer can be divided into at least two major types, microsatellite instability (MSI) or chromosomal instability (CIN). Although initially felt to be mutually exclusive, recent evidence suggests that there may be overlap between the two. The aim of this study was to identify chromosomal alterations at high resolution in sporadic colon cancers with high-level microsatellite instability (MSI-H) and to compare them to those present in a set of matched microsatellite stable (MSS) tumors. Experimental Design: Array-based comparative genomic hybridization was used to analyze a set of 23 sporadic MSI-H and 23 MSS colon cancers matched for location, gender, stage, and age. The arrays consisted of 2,464 bacterial artificial chromosome clones. Results: MSI and MSS colon cancers differed significantly with respect to frequency and type of chromosomal alterations. The median fraction of genome altered was lower among MSI-H tumors than MSS tumors (2.8{\%} versus 30.7{\%}, P = 0.00006). However, the MSI-H tumors displayed a range of genomic alterations, from the absence of detectable alterations to extensive alterations. Frequent alterations in MSI-H tumors included gains of chromosomes 8, 12, and 13, and loss of 15q14. In contrast, the most frequent alterations in MSS tumors were gains of 7, 13, 8q, and 20, and losses of 8p, 17p, and 18. A small, previously uncharacterized, genomic deletion on 16p13.2, found in 35{\%} of MSI-H and 21{\%} of MSS tumors, was confirmed by fluorescence in situ hybridization. Conclusion: MSI and CIN are not mutually exclusive forms of genomic instability in sporadic colon cancer, with MSI tumors also showing varying degrees of CIN.",
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AU - Trautmann, Karolin

AU - Terdiman, Jonathan P.

AU - French, Amy J.

AU - Roydasgupta, Ritu

AU - Sein, Nancy

AU - Kakar, Sanjay

AU - Fridlyand, Jane

AU - Snijders, Antoine M.

AU - Albertson, Donna

AU - Thibodeau, Stephen N.

AU - Waldman, Frederic M.

PY - 2006/11/1

Y1 - 2006/11/1

N2 - Purpose: The genomic instability in colon cancer can be divided into at least two major types, microsatellite instability (MSI) or chromosomal instability (CIN). Although initially felt to be mutually exclusive, recent evidence suggests that there may be overlap between the two. The aim of this study was to identify chromosomal alterations at high resolution in sporadic colon cancers with high-level microsatellite instability (MSI-H) and to compare them to those present in a set of matched microsatellite stable (MSS) tumors. Experimental Design: Array-based comparative genomic hybridization was used to analyze a set of 23 sporadic MSI-H and 23 MSS colon cancers matched for location, gender, stage, and age. The arrays consisted of 2,464 bacterial artificial chromosome clones. Results: MSI and MSS colon cancers differed significantly with respect to frequency and type of chromosomal alterations. The median fraction of genome altered was lower among MSI-H tumors than MSS tumors (2.8% versus 30.7%, P = 0.00006). However, the MSI-H tumors displayed a range of genomic alterations, from the absence of detectable alterations to extensive alterations. Frequent alterations in MSI-H tumors included gains of chromosomes 8, 12, and 13, and loss of 15q14. In contrast, the most frequent alterations in MSS tumors were gains of 7, 13, 8q, and 20, and losses of 8p, 17p, and 18. A small, previously uncharacterized, genomic deletion on 16p13.2, found in 35% of MSI-H and 21% of MSS tumors, was confirmed by fluorescence in situ hybridization. Conclusion: MSI and CIN are not mutually exclusive forms of genomic instability in sporadic colon cancer, with MSI tumors also showing varying degrees of CIN.

AB - Purpose: The genomic instability in colon cancer can be divided into at least two major types, microsatellite instability (MSI) or chromosomal instability (CIN). Although initially felt to be mutually exclusive, recent evidence suggests that there may be overlap between the two. The aim of this study was to identify chromosomal alterations at high resolution in sporadic colon cancers with high-level microsatellite instability (MSI-H) and to compare them to those present in a set of matched microsatellite stable (MSS) tumors. Experimental Design: Array-based comparative genomic hybridization was used to analyze a set of 23 sporadic MSI-H and 23 MSS colon cancers matched for location, gender, stage, and age. The arrays consisted of 2,464 bacterial artificial chromosome clones. Results: MSI and MSS colon cancers differed significantly with respect to frequency and type of chromosomal alterations. The median fraction of genome altered was lower among MSI-H tumors than MSS tumors (2.8% versus 30.7%, P = 0.00006). However, the MSI-H tumors displayed a range of genomic alterations, from the absence of detectable alterations to extensive alterations. Frequent alterations in MSI-H tumors included gains of chromosomes 8, 12, and 13, and loss of 15q14. In contrast, the most frequent alterations in MSS tumors were gains of 7, 13, 8q, and 20, and losses of 8p, 17p, and 18. A small, previously uncharacterized, genomic deletion on 16p13.2, found in 35% of MSI-H and 21% of MSS tumors, was confirmed by fluorescence in situ hybridization. Conclusion: MSI and CIN are not mutually exclusive forms of genomic instability in sporadic colon cancer, with MSI tumors also showing varying degrees of CIN.

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