Molecular diagnosis of familial adenomatous polyposis

Steven M. Powell, Gloria M Petersen, Anne J. Krush, Susan Booker, Jin Jen, Francis M. Giardiello, Stanley R. Hamilton, Bert Vogelstein, Kenneth W. Kinzler

Research output: Contribution to journalArticle

566 Citations (Scopus)

Abstract

Background. Familial adenomatous polyposis is an inherited disease characterized by multiple colorectal tumors. The diagnosis has classically been based on the detection of multiple colorectal adenomas. The recent identification of germline mutations of the APC gene in patients with familial adenomatous polyposis makes presymptomatic molecular diagnosis possible, but the widespread distribution of the many mutations within this very large gene have heretofore made the search for such mutations impractical. We describe a novel approach that allows molecular genetic diagnosis in the majority of patients with the disease. Methods. We screened 62 unrelated patients from the Johns Hopkins Familial Adenomatous Polyposis Registry for germline APC mutations. Primary screening was accomplished by analysis of protein synthesized in vitro from surrogate APC genes. In addition, the relative amount of transcript from each APC allele was determined with an allele-specific-expression assay. Results. The protein assay revealed truncated protein in 51 of the 62 patients (82 percent). In 3 of the 11 remaining patients, the allele-specific-expression assay revealed significantly reduced expression of one allele of the APC gene. The use of these two assays in combination successfully identified germline APC mutations in 87 percent of the 62 patients. Conclusions. The protein and allele-specific-expression assays provide a practical and sensitive method for molecular diagnosis of familial adenomatous polyposis. This approach will facilitate care, allowing routine testing of subjects at risk and genetic confirmation of spontaneous mutations.

Original languageEnglish (US)
Pages (from-to)1982-1987
Number of pages6
JournalNew England Journal of Medicine
Volume329
Issue number27
StatePublished - Dec 30 1993
Externally publishedYes

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Adenomatous Polyposis Coli
APC Genes
Alleles
Germ-Line Mutation
Mutation
Proteins
Adenoma
Registries
Molecular Biology
Colorectal Neoplasms
Genes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Powell, S. M., Petersen, G. M., Krush, A. J., Booker, S., Jen, J., Giardiello, F. M., ... Kinzler, K. W. (1993). Molecular diagnosis of familial adenomatous polyposis. New England Journal of Medicine, 329(27), 1982-1987.

Molecular diagnosis of familial adenomatous polyposis. / Powell, Steven M.; Petersen, Gloria M; Krush, Anne J.; Booker, Susan; Jen, Jin; Giardiello, Francis M.; Hamilton, Stanley R.; Vogelstein, Bert; Kinzler, Kenneth W.

In: New England Journal of Medicine, Vol. 329, No. 27, 30.12.1993, p. 1982-1987.

Research output: Contribution to journalArticle

Powell, SM, Petersen, GM, Krush, AJ, Booker, S, Jen, J, Giardiello, FM, Hamilton, SR, Vogelstein, B & Kinzler, KW 1993, 'Molecular diagnosis of familial adenomatous polyposis', New England Journal of Medicine, vol. 329, no. 27, pp. 1982-1987.
Powell SM, Petersen GM, Krush AJ, Booker S, Jen J, Giardiello FM et al. Molecular diagnosis of familial adenomatous polyposis. New England Journal of Medicine. 1993 Dec 30;329(27):1982-1987.
Powell, Steven M. ; Petersen, Gloria M ; Krush, Anne J. ; Booker, Susan ; Jen, Jin ; Giardiello, Francis M. ; Hamilton, Stanley R. ; Vogelstein, Bert ; Kinzler, Kenneth W. / Molecular diagnosis of familial adenomatous polyposis. In: New England Journal of Medicine. 1993 ; Vol. 329, No. 27. pp. 1982-1987.
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