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Whole-gene APC deletions cause classical familial adenomatous polyposis, but not attenuated polyposis or "multiple" colorectal adenomas.
Proc Natl Acad Sci U S A. 2002 Mar 05; 99(5):2954-8.PN

Abstract

Familial adenomatous polyposis (FAP) is a dominantly inherited colorectal tumor predisposition that results from germ-line mutations in the APC gene (chromosome 5q21). FAP shows substantial phenotypic variability: classical polyposis patients develop more than 100 colorectal adenomas, whereas those with attenuated polyposis (AAPC) have fewer than 100 adenomas. A further group of individuals, so-called "multiple" adenoma patients, have a phenotype like AAPC, with 3-99 polyps throughout the colorectum, but mostly have no demonstrable germ-line APC mutation. Routine mutation detection techniques fail to detect a pathogenic APC germ-line mutation in approximately 30% of patients with classical polyposis and 90% of those with AAPC/multiple adenomas. We have developed a real-time quantitative multiplex PCR assay to detect APC exon 14 deletions. When this technique was applied to a set of 60 classical polyposis and 143 AAPC/multiple adenoma patients with no apparent APC germ-line mutation, deletions were found exclusively in individuals with classical polyposis (7 of 60, 12%). Fine-mapping of the region suggested that the majority (6 of 7) of these deletions encompassed the entire APC locus, confirming that haploinsufficiency can result in a classical polyposis phenotype. Screening for germ-line deletions in APC mutation-negative individuals with classical polyposis seems warranted.

Authors+Show Affiliations

Molecular and Population Genetics Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

11867715

Citation

Sieber, O M., et al. "Whole-gene APC Deletions Cause Classical Familial Adenomatous Polyposis, but Not Attenuated Polyposis or "multiple" Colorectal Adenomas." Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 5, 2002, pp. 2954-8.
Sieber OM, Lamlum H, Crabtree MD, et al. Whole-gene APC deletions cause classical familial adenomatous polyposis, but not attenuated polyposis or "multiple" colorectal adenomas. Proc Natl Acad Sci USA. 2002;99(5):2954-8.
Sieber, O. M., Lamlum, H., Crabtree, M. D., Rowan, A. J., Barclay, E., Lipton, L., Hodgson, S., Thomas, H. J., Neale, K., Phillips, R. K., Farrington, S. M., Dunlop, M. G., Mueller, H. J., Bisgaard, M. L., Bulow, S., Fidalgo, P., Albuquerque, C., Scarano, M. I., Bodmer, W., ... Heinimann, K. (2002). Whole-gene APC deletions cause classical familial adenomatous polyposis, but not attenuated polyposis or "multiple" colorectal adenomas. Proceedings of the National Academy of Sciences of the United States of America, 99(5), 2954-8.
Sieber OM, et al. Whole-gene APC Deletions Cause Classical Familial Adenomatous Polyposis, but Not Attenuated Polyposis or "multiple" Colorectal Adenomas. Proc Natl Acad Sci USA. 2002 Mar 5;99(5):2954-8. PubMed PMID: 11867715.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Whole-gene APC deletions cause classical familial adenomatous polyposis, but not attenuated polyposis or "multiple" colorectal adenomas. AU - Sieber,O M, AU - Lamlum,H, AU - Crabtree,M D, AU - Rowan,A J, AU - Barclay,E, AU - Lipton,L, AU - Hodgson,S, AU - Thomas,H J W, AU - Neale,K, AU - Phillips,R K S, AU - Farrington,S M, AU - Dunlop,M G, AU - Mueller,H J, AU - Bisgaard,M L, AU - Bulow,S, AU - Fidalgo,P, AU - Albuquerque,C, AU - Scarano,M I, AU - Bodmer,W, AU - Tomlinson,I P M, AU - Heinimann,K, Y1 - 2002/02/26/ PY - 2002/2/28/pubmed PY - 2002/4/27/medline PY - 2002/2/28/entrez SP - 2954 EP - 8 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc. Natl. Acad. Sci. U.S.A. VL - 99 IS - 5 N2 - Familial adenomatous polyposis (FAP) is a dominantly inherited colorectal tumor predisposition that results from germ-line mutations in the APC gene (chromosome 5q21). FAP shows substantial phenotypic variability: classical polyposis patients develop more than 100 colorectal adenomas, whereas those with attenuated polyposis (AAPC) have fewer than 100 adenomas. A further group of individuals, so-called "multiple" adenoma patients, have a phenotype like AAPC, with 3-99 polyps throughout the colorectum, but mostly have no demonstrable germ-line APC mutation. Routine mutation detection techniques fail to detect a pathogenic APC germ-line mutation in approximately 30% of patients with classical polyposis and 90% of those with AAPC/multiple adenomas. We have developed a real-time quantitative multiplex PCR assay to detect APC exon 14 deletions. When this technique was applied to a set of 60 classical polyposis and 143 AAPC/multiple adenoma patients with no apparent APC germ-line mutation, deletions were found exclusively in individuals with classical polyposis (7 of 60, 12%). Fine-mapping of the region suggested that the majority (6 of 7) of these deletions encompassed the entire APC locus, confirming that haploinsufficiency can result in a classical polyposis phenotype. Screening for germ-line deletions in APC mutation-negative individuals with classical polyposis seems warranted. SN - 0027-8424 UR - https://www.unboundmedicine.com/medline/citation/11867715/Whole_gene_APC_deletions_cause_classical_familial_adenomatous_polyposis_but_not_attenuated_polyposis_or_"multiple"_colorectal_adenomas_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=11867715 DB - PRIME DP - Unbound Medicine ER -