Mechanisms underlying losses of heterozygosity in human colorectal cancers

Sam Thiagalingam, Steve Laken, James K V Willson, Sanford D. Markowitz, Kenneth W. Kinzler, Bert Vogelstein, Christoph Lengauer

Research output: Contribution to journalArticle

159 Citations (Scopus)

Abstract

Losses of heterozygosity are the most common molecular genetic alteration observed in human cancers. However, there have been few systematic studies to understand the mechanism(s) responsible for losses of heterozygosity in such tumors. Here we report a detailed investigation of the five chromosomes lost most frequently in human colorectal cancers. A total of 10,216 determinations were made with 88 microsatellite markers, revealing 245 chromosomal loss events. The mechanisms of loss were remarkably chromosome-specific. Some chromosomes displayed complete loss such as that predicted to result from mitotic nondisjunction. However, more than half of the losses were associated with losses of only part of a chromosome rather than a whole chromosome. Surprisingly, these losses were due largely to structural alterations rather than to mitotic recombination, break-induced replication, or gene conversion, suggesting novel mechanisms for the generation of much of the aneuploidy in this common tumor type.

Original languageEnglish (US)
Pages (from-to)2698-2702
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number5
DOIs
StatePublished - Feb 27 2001

Fingerprint

Loss of Heterozygosity
Colorectal Neoplasms
Chromosomes
Gene Conversion
Neoplasms
Aneuploidy
Microsatellite Repeats
Genetic Recombination
Molecular Biology

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Thiagalingam, S., Laken, S., Willson, J. K. V., Markowitz, S. D., Kinzler, K. W., Vogelstein, B., & Lengauer, C. (2001). Mechanisms underlying losses of heterozygosity in human colorectal cancers. Proceedings of the National Academy of Sciences of the United States of America, 98(5), 2698-2702. https://doi.org/10.1073/pnas.051625398

Mechanisms underlying losses of heterozygosity in human colorectal cancers. / Thiagalingam, Sam; Laken, Steve; Willson, James K V; Markowitz, Sanford D.; Kinzler, Kenneth W.; Vogelstein, Bert; Lengauer, Christoph.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 98, No. 5, 27.02.2001, p. 2698-2702.

Research output: Contribution to journalArticle

Thiagalingam, S, Laken, S, Willson, JKV, Markowitz, SD, Kinzler, KW, Vogelstein, B & Lengauer, C 2001, 'Mechanisms underlying losses of heterozygosity in human colorectal cancers', Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 5, pp. 2698-2702. https://doi.org/10.1073/pnas.051625398
Thiagalingam, Sam ; Laken, Steve ; Willson, James K V ; Markowitz, Sanford D. ; Kinzler, Kenneth W. ; Vogelstein, Bert ; Lengauer, Christoph. / Mechanisms underlying losses of heterozygosity in human colorectal cancers. In: Proceedings of the National Academy of Sciences of the United States of America. 2001 ; Vol. 98, No. 5. pp. 2698-2702.
@article{c9916695795a4aa6992d6494d2b9e760,
title = "Mechanisms underlying losses of heterozygosity in human colorectal cancers",
abstract = "Losses of heterozygosity are the most common molecular genetic alteration observed in human cancers. However, there have been few systematic studies to understand the mechanism(s) responsible for losses of heterozygosity in such tumors. Here we report a detailed investigation of the five chromosomes lost most frequently in human colorectal cancers. A total of 10,216 determinations were made with 88 microsatellite markers, revealing 245 chromosomal loss events. The mechanisms of loss were remarkably chromosome-specific. Some chromosomes displayed complete loss such as that predicted to result from mitotic nondisjunction. However, more than half of the losses were associated with losses of only part of a chromosome rather than a whole chromosome. Surprisingly, these losses were due largely to structural alterations rather than to mitotic recombination, break-induced replication, or gene conversion, suggesting novel mechanisms for the generation of much of the aneuploidy in this common tumor type.",
author = "Sam Thiagalingam and Steve Laken and Willson, {James K V} and Markowitz, {Sanford D.} and Kinzler, {Kenneth W.} and Bert Vogelstein and Christoph Lengauer",
year = "2001",
month = "2",
day = "27",
doi = "10.1073/pnas.051625398",
language = "English (US)",
volume = "98",
pages = "2698--2702",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "5",

}

TY - JOUR

T1 - Mechanisms underlying losses of heterozygosity in human colorectal cancers

AU - Thiagalingam, Sam

AU - Laken, Steve

AU - Willson, James K V

AU - Markowitz, Sanford D.

AU - Kinzler, Kenneth W.

AU - Vogelstein, Bert

AU - Lengauer, Christoph

PY - 2001/2/27

Y1 - 2001/2/27

N2 - Losses of heterozygosity are the most common molecular genetic alteration observed in human cancers. However, there have been few systematic studies to understand the mechanism(s) responsible for losses of heterozygosity in such tumors. Here we report a detailed investigation of the five chromosomes lost most frequently in human colorectal cancers. A total of 10,216 determinations were made with 88 microsatellite markers, revealing 245 chromosomal loss events. The mechanisms of loss were remarkably chromosome-specific. Some chromosomes displayed complete loss such as that predicted to result from mitotic nondisjunction. However, more than half of the losses were associated with losses of only part of a chromosome rather than a whole chromosome. Surprisingly, these losses were due largely to structural alterations rather than to mitotic recombination, break-induced replication, or gene conversion, suggesting novel mechanisms for the generation of much of the aneuploidy in this common tumor type.

AB - Losses of heterozygosity are the most common molecular genetic alteration observed in human cancers. However, there have been few systematic studies to understand the mechanism(s) responsible for losses of heterozygosity in such tumors. Here we report a detailed investigation of the five chromosomes lost most frequently in human colorectal cancers. A total of 10,216 determinations were made with 88 microsatellite markers, revealing 245 chromosomal loss events. The mechanisms of loss were remarkably chromosome-specific. Some chromosomes displayed complete loss such as that predicted to result from mitotic nondisjunction. However, more than half of the losses were associated with losses of only part of a chromosome rather than a whole chromosome. Surprisingly, these losses were due largely to structural alterations rather than to mitotic recombination, break-induced replication, or gene conversion, suggesting novel mechanisms for the generation of much of the aneuploidy in this common tumor type.

UR - http://www.scopus.com/inward/record.url?scp=0035956878&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035956878&partnerID=8YFLogxK

U2 - 10.1073/pnas.051625398

DO - 10.1073/pnas.051625398

M3 - Article

VL - 98

SP - 2698

EP - 2702

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 5

ER -