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Singapore familial adenomatous polyposis (FAP) patients with classical adenomatous polyposis but undetectable APC mutations have accelerated cancer progression.
Am J Gastroenterol. 2006 Dec; 101(12):2810-7.AJ

Abstract

OBJECTIVES

Germline mutation in adenomatous polyposis coli (APC) is detected in up to 80% of familial adenomatous polyposis (FAP) patients worldwide. In this study, we evaluated clinical features and APC mutations of Singapore FAP patients and contrasted genotype-phenotype correlation with Caucasians from other regions of the world and between FAP patients with and without detectable APC mutations.

METHODS

We screened 242 members from 57 unrelated FAP families using a combination of cDNA protein truncation test, multiplex ligation-dependent probe amplification, and differential expression techniques.

RESULTS

APC germline mutations were detected in 50 families. In contrast to Caucasians, fundic gland polyposis in Singapore patients was associated with APC mutations throughout the coding region and osteomas were also not confined to codon 767-1573. There was also no FAP-associated hepatoblastoma or medullablastoma. APC mutation-negative patients from four families with mixed (adenomatous/hyperplastic/atypical juvenile) polyps were subsequently reclassified as hereditary mixed polyposis syndrome (HMPS) patients. APC mutation-negative patients with classical adenomatous polyposis were negative for MYH, beta-catenin, and Axin 1 mutations. These patients had a significantly older age at diagnosis (P < 0.001) and more colorectal cancers (P= 0.017) than patients with APC mutations.

CONCLUSIONS

We achieved a 94% (50/53) APC mutation detection rate via a combination of techniques, suggesting that the current detection rate is probably not exhaustive. Singapore patients have some features similar to and other features distinct from Caucasians. Furthermore, APC mutation-negative patients have accelerated cancer progression that merits closer surveillance.

Authors+Show Affiliations

Department of Colorectal Surgery, Singapore General Hospital, Singapore.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17026565

Citation

Cao, Xia, et al. "Singapore Familial Adenomatous Polyposis (FAP) Patients With Classical Adenomatous Polyposis but Undetectable APC Mutations Have Accelerated Cancer Progression." The American Journal of Gastroenterology, vol. 101, no. 12, 2006, pp. 2810-7.
Cao X, Hong Y, Eu KW, et al. Singapore familial adenomatous polyposis (FAP) patients with classical adenomatous polyposis but undetectable APC mutations have accelerated cancer progression. Am J Gastroenterol. 2006;101(12):2810-7.
Cao, X., Hong, Y., Eu, K. W., Loi, C., & Cheah, P. Y. (2006). Singapore familial adenomatous polyposis (FAP) patients with classical adenomatous polyposis but undetectable APC mutations have accelerated cancer progression. The American Journal of Gastroenterology, 101(12), 2810-7.
Cao X, et al. Singapore Familial Adenomatous Polyposis (FAP) Patients With Classical Adenomatous Polyposis but Undetectable APC Mutations Have Accelerated Cancer Progression. Am J Gastroenterol. 2006;101(12):2810-7. PubMed PMID: 17026565.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Singapore familial adenomatous polyposis (FAP) patients with classical adenomatous polyposis but undetectable APC mutations have accelerated cancer progression. AU - Cao,Xia, AU - Hong,Yi, AU - Eu,Kong Weng, AU - Loi,Carol, AU - Cheah,Peh Yean, Y1 - 2006/10/06/ PY - 2006/10/10/pubmed PY - 2007/2/9/medline PY - 2006/10/10/entrez SP - 2810 EP - 7 JF - The American journal of gastroenterology JO - Am. J. Gastroenterol. VL - 101 IS - 12 N2 - OBJECTIVES: Germline mutation in adenomatous polyposis coli (APC) is detected in up to 80% of familial adenomatous polyposis (FAP) patients worldwide. In this study, we evaluated clinical features and APC mutations of Singapore FAP patients and contrasted genotype-phenotype correlation with Caucasians from other regions of the world and between FAP patients with and without detectable APC mutations. METHODS: We screened 242 members from 57 unrelated FAP families using a combination of cDNA protein truncation test, multiplex ligation-dependent probe amplification, and differential expression techniques. RESULTS: APC germline mutations were detected in 50 families. In contrast to Caucasians, fundic gland polyposis in Singapore patients was associated with APC mutations throughout the coding region and osteomas were also not confined to codon 767-1573. There was also no FAP-associated hepatoblastoma or medullablastoma. APC mutation-negative patients from four families with mixed (adenomatous/hyperplastic/atypical juvenile) polyps were subsequently reclassified as hereditary mixed polyposis syndrome (HMPS) patients. APC mutation-negative patients with classical adenomatous polyposis were negative for MYH, beta-catenin, and Axin 1 mutations. These patients had a significantly older age at diagnosis (P < 0.001) and more colorectal cancers (P= 0.017) than patients with APC mutations. CONCLUSIONS: We achieved a 94% (50/53) APC mutation detection rate via a combination of techniques, suggesting that the current detection rate is probably not exhaustive. Singapore patients have some features similar to and other features distinct from Caucasians. Furthermore, APC mutation-negative patients have accelerated cancer progression that merits closer surveillance. SN - 0002-9270 UR - https://www.unboundmedicine.com/medline/citation/17026565/Singapore_familial_adenomatous_polyposis__FAP__patients_with_classical_adenomatous_polyposis_but_undetectable_APC_mutations_have_accelerated_cancer_progression_ L2 - http://Insights.ovid.com/pubmed?pmid=17026565 DB - PRIME DP - Unbound Medicine ER -