BRAF mutations in aberrant crypt foci and hyperplastic polyposis

Robyn Beach, Annie On On Chan, Tsung Teh Wu, Jill A. White, Jeffrey S. Morris, Simon Lunagomez, Russell R. Broaddus, Jean Pierre J Issa, Stanley R. Hamilton, Asif Rashid

Research output: Contribution to journalArticle

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Abstract

Patients with hyperplastic polyposis have multiple hyperplastic polyps (HPs) and increased risk of colorectal carcinomas. Aberrant crypt foci (ACF) are postulated to be the earliest precursor lesions in colorectal carcinogenesis. We evaluated BRAF mutations by DNA sequencing in 53 ACF from patients with sporadic colorectal carcinomas and familial adenomatous polyposis, in 18 sporadic HPs from patients with resected colorectal cancer, and in 70 HPs, 4 serrated adenomas, 3 admixed hyperplastic-adenomatous polyps, 10 tubular adenomas, and 6 carcinomas from 17 patients with multiple/large HPs and/or hyperplastic polyposis. BRAF mutation status was compared with clinicopathological features and other genetic alterations by marginal logistic regression. BRAF mutation was present in only 2% of ACF and 6% of sporadic HPs. In contrast, BRAF mutation was present in 43% of HPs (P = 0.01 versus sporadic HPs), 75% of serrated adenomas, 33% of admixed hyperplastic-adenomatous polyps, 30% of tubular adenomas, and 33% of carcinomas from patients with multiple/large HPs and/or hyperplastic polyposis. BRAF mutation status in patients with multiple/large HPs and/or hyperplastic polyposis correlated with HPs from the same patient (odds ratio, 5.8; P = 0.0002) but associated with younger age (odds ratio, 0.83; P = 0.006 compared to older age), with a large HP (odds ratio, 22.5; P = 0.01 compared with patients with multiple HPs), with location of HPs in the right colon (odds ratio, 3.0; P = 0.03), and with methylation of the p16 gene and the MINT31 locus [odds ratio, 12.2 (P = 0.0001) and 4.4 (P = 0.02), respectively]. Our study shows that BRAF mutation status is heterogeneous among patients with multiple/large HPs and/or hyperplastic polyposis, suggesting differences in pathogenesis of HPs that indicate subsets within this phenotype.

Original languageEnglish (US)
Pages (from-to)1069-1075
Number of pages7
JournalAmerican Journal of Pathology
Volume166
Issue number4
StatePublished - Apr 2005
Externally publishedYes

Fingerprint

Aberrant Crypt Foci
Polyps
Mutation
Adenoma
Odds Ratio
Adenomatous Polyps
Colorectal Neoplasms
p16 Genes
Carcinoma
Adenomatous Polyposis Coli

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Beach, R., Chan, A. O. O., Wu, T. T., White, J. A., Morris, J. S., Lunagomez, S., ... Rashid, A. (2005). BRAF mutations in aberrant crypt foci and hyperplastic polyposis. American Journal of Pathology, 166(4), 1069-1075.

BRAF mutations in aberrant crypt foci and hyperplastic polyposis. / Beach, Robyn; Chan, Annie On On; Wu, Tsung Teh; White, Jill A.; Morris, Jeffrey S.; Lunagomez, Simon; Broaddus, Russell R.; Issa, Jean Pierre J; Hamilton, Stanley R.; Rashid, Asif.

In: American Journal of Pathology, Vol. 166, No. 4, 04.2005, p. 1069-1075.

Research output: Contribution to journalArticle

Beach, R, Chan, AOO, Wu, TT, White, JA, Morris, JS, Lunagomez, S, Broaddus, RR, Issa, JPJ, Hamilton, SR & Rashid, A 2005, 'BRAF mutations in aberrant crypt foci and hyperplastic polyposis', American Journal of Pathology, vol. 166, no. 4, pp. 1069-1075.
Beach R, Chan AOO, Wu TT, White JA, Morris JS, Lunagomez S et al. BRAF mutations in aberrant crypt foci and hyperplastic polyposis. American Journal of Pathology. 2005 Apr;166(4):1069-1075.
Beach, Robyn ; Chan, Annie On On ; Wu, Tsung Teh ; White, Jill A. ; Morris, Jeffrey S. ; Lunagomez, Simon ; Broaddus, Russell R. ; Issa, Jean Pierre J ; Hamilton, Stanley R. ; Rashid, Asif. / BRAF mutations in aberrant crypt foci and hyperplastic polyposis. In: American Journal of Pathology. 2005 ; Vol. 166, No. 4. pp. 1069-1075.
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