Evidence that genetic instability occurs at an early stage of colorectal tumorigenesis

Ie Ming Shih, W. Zhou, S. N. Goodman, C. Lengauer, Kenneth W Kinzler, Bert Vogelstein

Research output: Contribution to journalArticle

Abstract

Chromosomal instability is believed to be a common feature of most human tumors, but the stage at which such instability originates has not been defined. At the molecular level, chromosomal instability is characterized by allelic imbalance (AI), representing losses or gains of defined chromosomal regions. We have assessed AI in early colorectal tumors using newly developed methods for assessing AI in complex cell populations. A total of 32 adenomas of average size (2 mm; range, 1-3 mm) were studied. AI of chromosome 5q markers occurred in 55% of tumors analyzed, consistent with a gatekeeping role of the adenomatous polyposis coli tumor suppressor gene located at chromosomal position 5q21 AI was also detected in each of the other four chromosomes tested. The fractions of adenomas with AI of chromosomes 1p, 8p, 15q, and 18q were 10, 19, 28, and 28%, respectively. Over 90% of the tumors exhibited AI of at least one chromosome, and 67% had allelic imbalance of a chromosome other than 5q. These findings demonstrate that AI is a common event, even in very small tumors, and suggest that chromosomal instability occurs very early during colorectal neoplasia.

Original languageEnglish (US)
Pages (from-to)818-822
Number of pages5
JournalCancer Research
Volume61
Issue number3
StatePublished - 2001

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Allelic Imbalance
Carcinogenesis
Chromosomal Instability
Chromosomes
Neoplasms
Adenoma
Gatekeeping
Adenomatous Polyposis Coli
Tumor Suppressor Genes
Genetic Markers
Colorectal Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Evidence that genetic instability occurs at an early stage of colorectal tumorigenesis. / Shih, Ie Ming; Zhou, W.; Goodman, S. N.; Lengauer, C.; Kinzler, Kenneth W; Vogelstein, Bert.

In: Cancer Research, Vol. 61, No. 3, 2001, p. 818-822.

Research output: Contribution to journalArticle

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