The inducible prostaglandin biosynthetic enzyme, cyclooxygenase 2, is not mutated in patients with attenuated adenomatous polyposis coli

Lisa N. Spirio, Dan A. Dixon, Jennifer Robertson, Margaret Robertson, Jalene Barrows, Elie Traer, Randall W. Burt, Mark F. Leppert, Ray White, Stephen M. Prescott

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Germ-line mutations in the APC gene cause adenomatous polyposis coli (APC), a syndrome in which patients develop hundreds to thousands of precancerous adenomatous colorectal polyps. We described previously an attenuated form of APC (AAPC) resulting from very 5' mutations in APC in which affected patients exhibit fewer colorectal polyps and a later age of onset of colorectal cancer. However, because striking variations in colorectal polyp numbers occur among patients carrying identical AAPC mutations, alleles of another gene may modify the expression of the APC disease phenotype. We tested the hypothesis that loss of function of human cyclooxygenase 2 (COX-2), known to modify the APC phenotype in the Apc(Δ716) mouse, results in a decreased tumor burden in AAPC patients that develop very few colorectal polyps. Genomic DNA sequence analysis of human COX-2 revealed a silent mutation in exon 3 that was evenly distributed between two classes of patients with AAPC, those with small or large numbers of colorectal polyps. We also found no difference in levels of COX-2 mRNA in transformed blood lymphocytes among AAPC patients of either class or patients with classical APC, and no alterations that correlated with a lesser or greater number of colorectal polyps were detectable within approximately the first 1 kb of the promoter sequence. Therefore, mutation of the human COX-2 gene does not appear to be responsible for a low tumor burden among AAPC subjects.

Original languageEnglish (US)
Pages (from-to)4909-4912
Number of pages4
JournalCancer Research
Volume58
Issue number21
StatePublished - Nov 1 1998
Externally publishedYes

Fingerprint

Cyclooxygenase 2
Prostaglandins
Adenomatous Polyposis Coli
Polyps
Enzymes
Tumor Burden
Mutation
APC Genes
Phenotype
Adenomatous Polyps
Germ-Line Mutation
Attenuated Adenomatous Polyposis Coli
DNA Sequence Analysis
Age of Onset
Genes
Colorectal Neoplasms
Exons
Alleles
Lymphocytes
Messenger RNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Spirio, L. N., Dixon, D. A., Robertson, J., Robertson, M., Barrows, J., Traer, E., ... Prescott, S. M. (1998). The inducible prostaglandin biosynthetic enzyme, cyclooxygenase 2, is not mutated in patients with attenuated adenomatous polyposis coli. Cancer Research, 58(21), 4909-4912.

The inducible prostaglandin biosynthetic enzyme, cyclooxygenase 2, is not mutated in patients with attenuated adenomatous polyposis coli. / Spirio, Lisa N.; Dixon, Dan A.; Robertson, Jennifer; Robertson, Margaret; Barrows, Jalene; Traer, Elie; Burt, Randall W.; Leppert, Mark F.; White, Ray; Prescott, Stephen M.

In: Cancer Research, Vol. 58, No. 21, 01.11.1998, p. 4909-4912.

Research output: Contribution to journalArticle

Spirio, LN, Dixon, DA, Robertson, J, Robertson, M, Barrows, J, Traer, E, Burt, RW, Leppert, MF, White, R & Prescott, SM 1998, 'The inducible prostaglandin biosynthetic enzyme, cyclooxygenase 2, is not mutated in patients with attenuated adenomatous polyposis coli', Cancer Research, vol. 58, no. 21, pp. 4909-4912.
Spirio, Lisa N. ; Dixon, Dan A. ; Robertson, Jennifer ; Robertson, Margaret ; Barrows, Jalene ; Traer, Elie ; Burt, Randall W. ; Leppert, Mark F. ; White, Ray ; Prescott, Stephen M. / The inducible prostaglandin biosynthetic enzyme, cyclooxygenase 2, is not mutated in patients with attenuated adenomatous polyposis coli. In: Cancer Research. 1998 ; Vol. 58, No. 21. pp. 4909-4912.
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