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Science 5 January 1990:
Vol. 247. no. 4938, pp. 49 - 56
DOI: 10.1126/science.2294591
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Articles

Science, Vol 247, Issue 4938, 49-56
Copyright © 1990 by American Association for the Advancement of Science

articles

Identification of a chromosome 18q gene that is altered in colorectal cancers

ER Fearon, KR Cho, JM Nigro, SE Kern, JW Simons, JM Ruppert, Hamilton SR, AC Preisinger, G Thomas, KW Kinzler, and al. et

Oncology Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231.

Allelic deletions involving chromosome 18q occur in more than 70 percent of colorectal cancers. Such deletions are thought to signal the existence of a tumor suppressor gene in the affected region, but until now a candidate suppressor gene on this chromosomal arm had not been identified. A contiguous stretch of DNA comprising 370 kilobase pairs (kb) has now been cloned from a region of chromosome 18q suspected to reside near this gene. Potential exons in the 370-kb region were defined by human-rodent sequence identities, and the expression of potential exons was assessed by an "exon-connection" strategy based on the polymerase chain reaction. Expressed exons were used as probes for cDNA screening to obtain clones that encoded a portion of a gene termed DCC; this cDNA was encoded by at least eight exons within the 370-kb genomic region. The predicted amino acid sequence of the cDNA specified a protein with sequence similarity to neural cell adhesion molecules and other related cell surface glycoproteins. While the DCC gene was expressed in most normal tissues, including colonic mucosa, its expression was greatly reduced or absent in most colorectal carcinomas tested. Somatic mutations within the DCC gene observed in colorectal cancers included a homozygous deletion of the 5' end of the gene, a point mutation within one of the introns, and ten examples of DNA insertions within a 0.17-kb fragment immediately downstream of one of the exons. The DCC gene may play a role in the pathogenesis of human colorectal neoplasia, perhaps through alteration of the normal cell-cell interactions controlling growth.


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   Abstract »    PDF »
Netrin-1: Interaction with Deleted in Colorectal Cancer (DCC) and Alterations in Brain Tumors and Neuroblastomas.
J. A. Meyerhardt, K. Caca, B. C. Eckstrand, G. Hu, C. Lengauer, S. Banavali, A. T. Look, and E. R. Fearon (1999)
Cell Growth Differ. 10, 35-42
   Abstract »    Full Text »
Allelotype Analysis of Adult T-Cell Leukemia.
Y. Hatta, Y. Yamada, M. Tomonaga, J. W. Said, I. Miyosi, and H. P. Koeffler (1998)
Blood 92, 2113-2117
   Abstract »    Full Text »    PDF »
Comparative Genomic Hybridization Analysis of Nonfunctioning Pituitary Tumors.
M. Daniely, A. Aviram, E. F. Adams, M. Buchfelder, G. Barkai, R. Fahlbusch, B. Goldman, and E. Friedman (1998)
J. Clin. Endocrinol. Metab. 83, 1801-1805
   Abstract »    Full Text »
Factors Affecting Inverted Repeat Stimulation of Recombination and Deletion in Saccharomyces cerevisiae.
K. S. Lobachev, B. M. Shor, H. T. Tran, W. Taylor, J. D. Keen, M. A. Resnick, and D. A. Gordenin (1998)
Genetics 148, 1507-1524
   Abstract »    Full Text »    PDF »
Analysis of genomic alterations in benign, atypical, and anaplastic meningiomas: Toward a genetic model of meningioma progression.
R. G. Weber, J. Bostrom, M. Wolter, M. Baudis, V. P. Collins, G. Reifenberger, and P. Lichter (1997)
PNAS 94, 14719-14724
   Abstract »    Full Text »    PDF »
Deleted in Colorectal Carcinoma (DCC) Binds Heparin via Its Fifth Fibronectin Type III Domain.
K. L. Bennett, J. Bradshaw, T. Youngman, J. Rodgers, B. Greenfield, A. Aruffo, and P. S. Linsley (1997)
J. Biol. Chem. 272, 26940-26946
   Abstract »    Full Text »    PDF »
Mammalian homologs of seven in absentia regulate DCC via the ubiquitin-proteasome pathway.
G. Hu, S. Zhang, M. Vidal, J. L. Baer, T. Xu, and E. R. Fearon (1997)
Genes & Dev. 11, 2701-2714
   Abstract »    Full Text »    PDF »
Mouse mammary tumor virus/v-Ha-ras transgene-induced mammary tumors exhibit strain-specific allelic loss on mouse chromosome 4.
E. H. Radany, K. Hong, S. Kesharvarzi, E. S. Lander, and J. M. Bishop (1997)
PNAS 94, 8664-8669
   Abstract »    Full Text »    PDF »
CDO: An Oncogene-, Serum-, and Anchorage-regulated Member of the Ig/Fibronectin Type III Repeat Family.
J.-S. Kang, M. Gao, J. L. Feinleib, P. D. Cotter, S. N. Guadagno, and R. S. Krauss (1997)
J. Cell Biol. 138, 203-213
   Abstract »    Full Text »    PDF »
Frequent Loss of Heterozygosity on Chromosome Arm 18q in Squamous Cell Carcinomas: Identification of 2 Regions of Loss--18q11.1-q12.3 and 18q21.1-q23.
J. W. Jones, J. R. Raval, T. F. Beals, M. J. Worsham, D. L. Van Dyke, R. M. Esclamado, G. T. Wolf, C. R. Bradford, T. Miller, and T. E. Carey (1997)
Arch Otolaryngol Head Neck Surg 123, 610-614
   Abstract »    PDF »
Molecules making waves in axon guidance..
A Varela-Echavarria and S Guthrie (1997)
Genes & Dev. 11, 545-557
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Guidance of Developing Axons by Netrin-1 and Its Receptors.
E.D. Leonardo, L. Hinck, M. Masu, K. Keino-Masu, A. Fazeli, E. T. Stoeckli, S.L. Ackerman, R.A. Weinberg, and M. Tessier-Lavigne (1997)
Cold Spring Harb Symp Quant Biol 62, 467-478
   Abstract »    PDF »
The DCC Protein and Prognosis in Colorectal Cancer.
D. Shibata, M. A. Reale, P. Lavin, M. Silverman, E. R. Fearon, G. Steele, J. M. Jessup, M. Loda, and I. C. Summerhayes (1996)
N. Engl. J. Med. 335, 1727-1732
   Abstract »    Full Text »    PDF »
Direct cDNA selection with DNA microdissected from mouse chromosome 16: isolation of novel clones and construction of a partial transcription map of the C3-C4 region..
J Wei, M E Hodes, Y Wang, Y Feng, B Ghetti, and S R Dlouhy (1996)
Genome Res. 6, 678-687
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Screening for Colorectal Cancer.
N. W. Toribara and M. H. Sleisenger (1995)
N. Engl. J. Med. 332, 861-867
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Allelic Loss of Chromosome 18q and Prognosis in Colorectal Cancer.
J. Jen, H. Kim, S. Piantadosi, Z.-F. Liu, R. C. Levitt, P. Sistonen, K. W. Kinzler, B. Vogelstein, and S. R. Hamilton (1994)
N. Engl. J. Med. 331, 213-221
   Abstract »    Full Text »
The DCC gene product in cellular differentiation and colorectal tumorigenesis..
L Hedrick, K R Cho, E R Fearon, T C Wu, K W Kinzler, and B Vogelstein (1994)
Genes & Dev. 8, 1174-1183
   Abstract »    PDF »


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