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Abstract

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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Published In

Science
Volume 253 | Issue 5020
9 August 1991

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Published in print: 9 August 1991

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Authors

Affiliations

Kenneth W. Kinzler
Molecular Genetics Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD 21231.
Mef C. Nilbert
Molecular Genetics Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD 21231.
Li-Kuo Su
Molecular Genetics Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD 21231.
Bert Vogelstein
Molecular Genetics Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD 21231.
Tracy M. Bryan
Molecular Genetics Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD 21231.
Daniel B. Levy
Molecular Genetics Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD 21231.
Kelly J. Smith
Molecular Genetics Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD 21231.
Antonette C. Preisinger
Molecular Genetics Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD 21231.
Philip Hedge
ICI Pharmaceuticals, Cheshire, United Kingdom SK10 4TG.
Douglas McKechnie
ICI Pharmaceuticals, Cheshire, United Kingdom SK10 4TG.
Rachel Finniear
ICI Pharmaceuticals, Cheshire, United Kingdom SK10 4TG.
Alex Markham
ICI Pharmaceuticals, Cheshire, United Kingdom SK10 4TG.
John Groffen
Department of Pathology, Children's Hospital of Los Angeles, Los Angeles, CA 90027.
Mark S. Boguski
National Center for Biotechnology Information, National Library of Medicine, Bethesda, MD 20894
Stephen F. Altschul
National Center for Biotechnology Information, National Library of Medicine, Bethesda, MD 20894
Akira Horii
Department of Biochemistry, Cancer Institute, Tokyo 170, Japan.
Hiroshi Ando
Department of Biochemistry, Cancer Institute, Tokyo 170, Japan.
Yasuo Miyoshi
Department of Biochemistry, Cancer Institute, Tokyo 170, Japan.
Yoshio Miki
Department of Biochemistry, Cancer Institute, Tokyo 170, Japan.
Isamu Nishisho
Department of Biochemistry, Cancer Institute, Tokyo 170, Japan.
Yusuke Nakamura
Department of Biochemistry, Cancer Institute, Tokyo 170, Japan.

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