Whole-gene APC deletions cause classical familial adenomatous polyposis, but not attenuated polyposis or "multiple" colorectal adenomas

O M Sieber, H Lamlum, M D Crabtree, A J Rowan, E Barclay, L Lipton, S Hodgson, H J W Thomas, K Neale, R K S Phillips, S M Farrington, M G Dunlop, H J Mueller, M L Bisgaard, S Bulow, P Fidalgo, C Albuquerque, M I Scarano, W Bodmer, I P M TomlinsonK Heinimann

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.
Original languageEnglish
Pages (from-to)2954-8
Number of pages5
JournalProceedings of the National Academy of Sciences (PNAS)
Issue number5
Publication statusPublished - 5 Mar 2002

Keywords / Materials (for Non-textual outputs)

  • Adenoma
  • Adenomatous Polyposis Coli
  • Adenomatous Polyposis Coli Protein
  • Colorectal Neoplasms
  • DNA Primers
  • Exons
  • Gene Deletion
  • Genes, APC
  • Genetic Testing
  • Humans
  • Polymerase Chain Reaction


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