APC mutations occur early during colorectal tumorigenesis

Steven M. Powell, Nathan Zilz, Yasmin Beazer-Barclay, Tracy M. Bryan, Stanley R. Hamilton, Stephen N Thibodeau, Bert Vogelstein, Kenneth W. Kinzler

Research output: Contribution to journalArticle

1495 Citations (Scopus)

Abstract

HUMAN tumorigenesis is associated with the accumulating of mutations both in oncogenes and in tumour suppressor genes1-3. But in no common adult cancer have the mutations that are critical in the early stages of the tumorigenic process been defined. We have attempted to determine if mutations of the APC gene play such a role in human colorectal tumours, which evolve from small benign tumours (adenomas) to larger malignant tumours (carcinomas) over the course of several decades. Here we report that sequence analysis of 41 colorectal tumours revealed that the majority of colorectal carcinomas (60%) and adenomas (63%) contained a mutated APC gene. Furthermore, the APC gene met two criteria of importance for tumour initiation. First, mutations of this gene were found in the earliest tumours that could be analysed, including adenomas as small as 0.5 cm in diameter. Second, the frequency of such mutations remained constant as tumours progressed from benign to malignant stages. These data provide strong evidence that mutations of the APC gene play a major role in the early development of colorectal neoplasms.

Original languageEnglish (US)
Pages (from-to)235-237
Number of pages3
JournalNature
Volume359
Issue number6392
StatePublished - Sep 17 1992

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Carcinogenesis
APC Genes
Mutation
Colorectal Neoplasms
Neoplasms
Adenoma
Mutation Rate
Oncogenes
Sequence Analysis
Carcinoma
Genes

ASJC Scopus subject areas

  • General

Cite this

Powell, S. M., Zilz, N., Beazer-Barclay, Y., Bryan, T. M., Hamilton, S. R., Thibodeau, S. N., ... Kinzler, K. W. (1992). APC mutations occur early during colorectal tumorigenesis. Nature, 359(6392), 235-237.

APC mutations occur early during colorectal tumorigenesis. / Powell, Steven M.; Zilz, Nathan; Beazer-Barclay, Yasmin; Bryan, Tracy M.; Hamilton, Stanley R.; Thibodeau, Stephen N; Vogelstein, Bert; Kinzler, Kenneth W.

In: Nature, Vol. 359, No. 6392, 17.09.1992, p. 235-237.

Research output: Contribution to journalArticle

Powell, SM, Zilz, N, Beazer-Barclay, Y, Bryan, TM, Hamilton, SR, Thibodeau, SN, Vogelstein, B & Kinzler, KW 1992, 'APC mutations occur early during colorectal tumorigenesis', Nature, vol. 359, no. 6392, pp. 235-237.
Powell SM, Zilz N, Beazer-Barclay Y, Bryan TM, Hamilton SR, Thibodeau SN et al. APC mutations occur early during colorectal tumorigenesis. Nature. 1992 Sep 17;359(6392):235-237.
Powell, Steven M. ; Zilz, Nathan ; Beazer-Barclay, Yasmin ; Bryan, Tracy M. ; Hamilton, Stanley R. ; Thibodeau, Stephen N ; Vogelstein, Bert ; Kinzler, Kenneth W. / APC mutations occur early during colorectal tumorigenesis. In: Nature. 1992 ; Vol. 359, No. 6392. pp. 235-237.
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