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Science 9 August 1991:
Vol. 253. no. 5020, pp. 661 - 665
DOI: 10.1126/science.1651562
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Articles

Science, Vol 253, Issue 5020, 661-665
Copyright © 1991 by American Association for the Advancement of Science

articles

Identification of FAP locus genes from chromosome 5q21

KW Kinzler, MC Nilbert, LK Su, B Vogelstein, TM Bryan, DB Levy, KJ Smith, AC Preisinger, P Hedge, D McKechnie, and al. et

Molecular Genetics Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD 21231.

Recent studies suggest that one or more genes on chromosome 5q21 are important for the development of colorectal cancers, particularly those associated with familial adenomatous polyposis (FAP). To facilitate the identification of genes from this locus, a portion of the region that is tightly linked to FAP was cloned. Six contiguous stretches of sequence (contigs) containing approximately 5.5 Mb of DNA were isolated. Subclones from these contigs were used to identify and position six genes, all of which were expressed in normal colonic mucosa. Two of these genes (APC and MCC) are likely to contribute to colorectal tumorigenesis. The MCC gene had previously been identified by virtue of its mutation in human colorectal tumors. The APC gene was identified in a contig initiated from the MCC gene and was found to encode an unusually large protein. These two closely spaced genes encode proteins predicted to contain coiled-coil regions. Both genes were also expressed in a wide variety of tissues. Further studies of MCC and APC and their potential interaction should prove useful for understanding colorectal neoplasia.


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K. Heinimann, A. Thompson, A. Locher, T. Furlanetto, E. Bader, A. Wolf, R. Meier, K. Walter, P. Bauerfeind, G. Marra, et al. (2001)
Cancer Res. 61, 7616-7622
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R S Houlston (2001)
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H. Fischer, R. Stenling, C. Rubio, and A. Lindblom (2001)
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Familial Occurrence of Nonmedullary Thyroid Cancer: A Population-based Study of 5673 First-Degree Relatives of Thyroid Cancer Patients from Norway.
L. Frich, E. Glattre, and L. A. Akslen (2001)
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A Mammalian Two-Hybrid System for Adenomatous Polyposis Coli-Mutated Colon Cancer Therapeutics.
K. Wakita, O. Tetsu, and F. McCormick (2001)
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Submicroscopic deletions of the APC gene: a frequent cause of familial adenomatous polyposis that may be overlooked by conventional mutation scanning.
K. J FLINTOFF, E. SHERIDAN, G. TURNER, C. E CHU, and G. R TAYLOR (2001)
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Organizing Cancer Genetics Programs: The Swiss Model.
G. Pichert and R. A. Stahel (2000)
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Characterization of Hereditary Nonpolyposis Colorectal Cancer Families From a Population-Based Series of Cases.
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P. Polakis (2000)
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Identification and Fine Mapping of a Region Showing a High Frequency of Allelic Imbalance on Chromosome 16q23.2 That Corresponds to a Prostate Cancer Susceptibility Locus.
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The Effect of Celecoxib, a Cyclooxygenase-2 Inhibitor, in Familial Adenomatous Polyposis.
G. Steinbach, P. M. Lynch, R. K.S. Phillips, M. H. Wallace, E. Hawk, G. B. Gordon, N. Wakabayashi, B. Saunders, Y. Shen, T. Fujimura, et al. (2000)
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Somatic Mutations of the APC Gene in Primary Breast Cancers.
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Biology of the Adenomatous Polyposis Coli Tumor Suppressor.
K. H. Goss and J. Groden (2000)
J. Clin. Oncol. 18, 1967-1979
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A Novel Non-pathogenetic Polymorphism of the APC Gene in a Patient with Familial Adenomatous Polyposis Coli.
Y. Ogiso, I. Ueno, M. Fujimori, Y. Fukushima, and T. Katsuyama (2000)
Jpn. J. Clin. Oncol. 30, 204-206
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Molecular Linkage Underlying Microtubule Orientation Toward Cortical Sites in Yeast.
W. S. Korinek, M. J. Copeland, A. Chaudhuri, and J. Chant (2000)
Science 287, 2257-2259
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The Relationship Between Frequencies of Extracolonic Manifestations and the Position of APC Germline Mutation in Patients with Familial Adenomatous Polyposis.
M. Enomoto, M. Konishi, T. Iwama, J. Utsunomiya, K.-i. Sugihara, and M. Miyaki (2000)
Jpn. J. Clin. Oncol. 30, 82-88
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Deletion and duplication of the adenomatous polyposis coli gene resulting from an interchromosomal insertion involving 5(q22q23.3) in the father.
R J HASTINGS, E C SVENNEVIK, B SETTERFIELD, D WELLS, J D A DELHANTY, and H MACKINNON (2000)
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Germline Mutations of the APC Gene in Patients with Familial Adenomatous Polyposis-Associated Thyroid Carcinoma: Results from a European Cooperative Study.
F. Cetta, G. Montalto, M. Gori, M. C. Curia, A. Cama, and S. Olschwang (2000)
J. Clin. Endocrinol. Metab. 85, 286-292
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