Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 15 March 1991:
Vol. 251. no. 4999, pp. 1366 - 1370
DOI: 10.1126/science.1848370
Prev | Table of Contents | Next

Articles

Science, Vol 251, Issue 4999, 1366-1370
Copyright © 1991 by American Association for the Advancement of Science

articles

Identification of a gene located at chromosome 5q21 that is mutated in colorectal cancers

KW Kinzler, MC Nilbert, B Vogelstein, TM Bryan, DB Levy, KJ Smith, AC Preisinger, Hamilton SR, P Hedge, A Markham, and al. et

Molecular Genetics Laboratory, Johns Hopkins Oncology Center, Baltimore, MD 21231.

Recent studies have suggested the existence of a tumor suppressor gene located at chromosome region 5q21. DNA probes from this region were used to study a panel of sporadic colorectal carcinomas. One of these probes, cosmid 5.71, detected a somatically rearranged restriction fragment in the DNA from a single tumor. Further analysis of the 5.71 cosmid revealed two regions that were highly conserved in rodent DNA. These sequences were used to identify a gene, MCC (mutated in colorectal cancer), which encodes an 829-amino acid protein with a short region of similarity to the G protein-coupled m3 muscarinic acetylcholine receptor. The rearrangement in the tumor disrupted the coding region of the MCC gene. Moreover, two colorectal tumors were found with somatically acquired point mutations in MCC that resulted in amino acid substitutions. MCC is thus a candidate for the putative colorectal tumor suppressor gene located at 5q21. Further studies will be required to determine whether the gene is mutated in other sporadic tumors or in the germ line of patients with an inherited predisposition to colonic tumorigenesis.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
The Role of Pediatricians in Families with a History of Familial Adenomatous Polyposis.
A. M. Augustyn and R. Wallerstein (2009)
Clinical Pediatrics 48, 623-626
   Abstract »    PDF »
A Transposon-Based Genetic Screen in Mice Identifies Genes Altered in Colorectal Cancer.
T. K. Starr, R. Allaei, K. A. T. Silverstein, R. A. Staggs, A. L. Sarver, T. L. Bergemann, M. Gupta, M. G. O'Sullivan, I. Matise, A. J. Dupuy, et al. (2009)
Science 323, 1747-1750
   Abstract »    Full Text »    PDF »
Human Colon Cancer Stem Cells: A New Paradigm in Gastrointestinal Oncology.
B. M. Boman and E. Huang (2008)
J. Clin. Oncol. 26, 2828-2838
   Abstract »    Full Text »    PDF »
Familial Colorectal Cancer: A Genetics Treasure Trove for Medical Discovery.
B. Pasche (2008)
JAMA 299, 2564-2565
   Full Text »    PDF »
Cross-Species Comparison of Human and Mouse Intestinal Polyps Reveals Conserved Mechanisms in Adenomatous Polyposis Coli (APC)-Driven Tumorigenesis.
C. Gaspar, J. Cardoso, P. Franken, L. Molenaar, H. Morreau, G. Moslein, J. Sampson, J. M. Boer, R. X. de Menezes, and R. Fodde (2008)
Am. J. Pathol. 172, 1363-1380
   Abstract »    Full Text »    PDF »
Cyclooxygenase-2 Inhibition Inhibits c-Met Kinase Activity and Wnt Activity in Colon Cancer.
J. B. Tuynman, L. Vermeulen, E. M. Boon, K. Kemper, A. H. Zwinderman, M. P. Peppelenbosch, and D. J. Richel (2008)
Cancer Res. 68, 1213-1220
   Abstract »    Full Text »    PDF »
Adenomatous polyposis coli (APC): a multi-functional tumor suppressor gene.
K. Aoki and M. M. Taketo (2007)
J. Cell Sci. 120, 3327-3335
   Abstract »    Full Text »    PDF »
Integration of Somatic Deletion Analysis of Prostate Cancers and Germline Linkage Analysis of Prostate Cancer Families Reveals Two Small Consensus Regions for Prostate Cancer Genes at 8p.
B.-l. Chang, W. Liu, J. Sun, L. Dimitrov, T. Li, A. R. Turner, S. L. Zheng, W. B. Isaacs, and J. Xu (2007)
Cancer Res. 67, 4098-4103
   Abstract »    Full Text »    PDF »
Overexpression of Glycosylphosphatidylinositol (GPI) Transamidase Subunits Phosphatidylinositol Glycan Class T and/or GPI Anchor Attachment 1 Induces Tumorigenesis and Contributes to Invasion in Human Breast Cancer..
G. Wu, Z. Guo, A. Chatterjee, X. Huang, E. Rubin, F. Wu, E. Mambo, X. Chang, M. Osada, M. Sook Kim, et al. (2006)
Cancer Res. 66, 9829-9836
   Abstract »    Full Text »    PDF »
Unraveling the Chromosomal Aberrations of Head and Neck Squamous Cell Carcinoma: A Review.
H. S. Patmore, L. Cawkwell, N. D. Stafford, and J. Greenman (2005)
Ann. Surg. Oncol. 12, 831-842
   Abstract »    Full Text »    PDF »
DRO1, a Gene Down-regulated by Oncogenes, Mediates Growth Inhibition in Colon and Pancreatic Cancer Cells.
G. T. Bommer, C. Jager, E.-M. Durr, S. Baehs, S. T. Eichhorst, T. Brabletz, G. Hu, T. Frohlich, G. Arnold, D. C. Kress, et al. (2005)
J. Biol. Chem. 280, 7962-7975
   Abstract »    Full Text »    PDF »
The links between axin and carcinogenesis.
S Salahshor and J R Woodgett (2005)
J. Clin. Pathol. 58, 225-236
   Abstract »    Full Text »    PDF »
Genetic basis of variation in adenoma multiplicity in ApcMin/+ Mom1S mice.
J. Haines, V. Johnson, K. Pack, N. Suraweera, P. Slijepcevic, E. Cabuy, M. Coster, M. Ilyas, J. Wilding, O. Sieber, et al. (2005)
PNAS 102, 2868-2873
   Abstract »    Full Text »    PDF »
Identification of Specific Cellular Genes Up-Regulated Late in Adenovirus Type 12 Infection.
A. Dorn, H. Zhao, F. Granberg, M. Hosel, D. Webb, C. Svensson, U. Pettersson, and W. Doerfler (2005)
J. Virol. 79, 2404-2412
   Abstract »    Full Text »    PDF »
Apoptosis and colorectal cancer.
A J M Watson (2004)
Gut 53, 1701-1709
   Full Text »    PDF »
Global Gene Expression Profile of Nasopharyngeal Carcinoma by Laser Capture Microdissection and Complementary DNA Microarrays.
V. Sriuranpong, A. Mutirangura, J. W. Gillespie, V. Patel, P. Amornphimoltham, A. A. Molinolo, V. Kerekhanjanarong, S. Supanakorn, P. Supiyaphun, S. Rangdaeng, et al. (2004)
Clin. Cancer Res. 10, 4944-4958
   Abstract »    Full Text »    PDF »
Evolutionary dynamics of tumor suppressor gene inactivation.
M. A. Nowak, F. Michor, N. L. Komarova, and Y. Iwasa (2004)
PNAS 101, 10635-10638
   Abstract »    Full Text »    PDF »
Chemoprevention of Cancer.
A. S. Tsao, E. S. Kim, and W. K. Hong (2004)
CA Cancer J Clin 54, 150-180
   Abstract »    Full Text »    PDF »
The Correlation of Microsatellite Instability and Tumor-infiltrating Lymphocytes in Hereditary Non-polyposis Colorectal Cancer (HNPCC) and Sporadic Colorectal Cancers: the Significance of Different Types of Lymphocyte Infiltration.
N. Takemoto, F. Konishi, K. Yamashita, M. Kojima, T. Furukawa, Y. Miyakura, K. Shitoh, and H. Nagai (2004)
Jpn. J. Clin. Oncol. 34, 90-98
   Abstract »    Full Text »    PDF »
Lymphodepletion in the ApcMin/+ mouse model of intestinal tumorigenesis.
P. L. Coletta, A. M. Muller, E. A. Jones, B. Muhl, S. Holwell, D. Clarke, J. L. Meade, G. P. Cook, G. Hawcroft, F. Ponchel, et al. (2004)
Blood 103, 1050-1058
   Abstract »    Full Text »    PDF »
Alterations of the Birt-Hogg-Dube gene (BHD) in sporadic colorectal tumours.
K Kahnoski, S K Khoo, N T Nassif, J Chen, G P Lobo, E Segelov, and B T Teh (2003)
J. Med. Genet. 40, 511-515
   Full Text »    PDF »
Digital karyotyping.
T.-L. Wang, C. Maierhofer, M. R. Speicher, C. Lengauer, B. Vogelstein, K. W. Kinzler, and V. E. Velculescu (2002)
PNAS 99, 16156-16161
   Abstract »    Full Text »    PDF »
Low-penetrance Genes and Their Involvement in Colorectal Cancer Susceptibility.
M. M. de Jong, I. M. Nolte, G. J. te Meerman, W. T. A. van der Graaf, E. G. E. de Vries, R. H. Sijmons, R. M. W. Hofstra, and J. H. Kleibeuker (2002)
Cancer Epidemiol. Biomarkers Prev. 11, 1332-1352
   Abstract »    Full Text »    PDF »
PC-SPES Inhibits Colon Cancer Growth in Vitro and in Vivo.
S. Huerta, J. R. Arteaga, R. W. Irwin, T. Ikezoe, D. Heber, and H. P. Koeffler (2002)
Cancer Res. 62, 5204-5209
   Abstract »    Full Text »    PDF »
1{alpha},25-(OH)2-D3 and Its Synthetic Analogue Decrease Tumor Load in the Apcmin Mouse.
S. Huerta, R. W. Irwin, D. Heber, V. L. W. Go, H. P. Koeffler, M. R. Uskokovic, and D. M. Harris (2002)
Cancer Res. 62, 741-746
   Abstract »    Full Text »    PDF »
Cell Density and Phosphorylation Control the Subcellular Localization of Adenomatous Polyposis Coli Protein.
F. Zhang, R. L. White, and K. L. Neufeld (2001)
Mol. Cell. Biol. 21, 8143-8156
   Abstract »    Full Text »    PDF »
Suppressor of Fused Negatively Regulates beta -Catenin Signaling.
X. Meng, R. Poon, X. Zhang, A. Cheah, Q. Ding, C.-c. Hui, and B. Alman (2001)
J. Biol. Chem. 276, 40113-40119
   Abstract »    Full Text »    PDF »
Nuclear Localization of {beta}-Catenin and Plakoglobin in Primary and Metastatic Human Colonic Carcinomas, Colonic Adenomas, and Normal Colon.
B. Lifschitz-Mercer, R. Amitai, B. B.-S. Maymon, L. Shechtman, B. Czernobilsky, L. Leider-Trejo, A. Ben-Ze'ev, and B. Geiger (2001)
International Journal of Surgical Pathology 9, 273-279
   Abstract »    PDF »
Decision analysis in the surgical treatment of patients with familial adenomatous polyposis: a Dutch-Scandinavian collaborative study including 659 patients.
H F A Vasen, P van Duijvendijk, E Buskens, C Bulow, J Bjork, H J Jarvinen, and S Bulow (2001)
Gut 49, 231-235
   Abstract »    Full Text »    PDF »
What we could do now: molecular pathology of colorectal cancer.
R S Houlston (2001)
Mol. Pathol. 54, 206-214
   Abstract »    Full Text »    PDF »
Biomarkers for Early Detection of Colon Cancer.
S. Srivastava, M. Verma, and D. E. Henson (2001)
Clin. Cancer Res. 7, 1118-1126
   Abstract »    Full Text »
Stabilized {beta}-Catenin Immortalizes Colonic Epithelial Cells.
R. A. Wagenaar, H. C. Crawford, and L. M. Matrisian (2001)
Cancer Res. 61, 2097-2104
   Abstract »    Full Text »
Apical Membrane Localization of the Adenomatous Polyposis Coli Tumor Suppressor Protein and Subcellular Distribution of the {beta}-Catenin Destruction Complex in Polarized Epithelial Cells.
A. Reinacher-Schick and B. M. Gumbiner (2001)
J. Cell Biol. 152, 491-502
   Abstract »    Full Text »    PDF »
Genome-wide Allelotyping of Lung Cancer Identifies New Regions of Allelic Loss, Differences between Small Cell Lung Cancer and Non-Small Cell Lung Cancer, and Loci Clustering.
L. Girard, S. Zöchbauer-Müller, A. K. Virmani, A. F. Gazdar, and J. D. Minna (2000)
Cancer Res. 60, 4894-4906
   Abstract »    Full Text »
APC mutations in sporadic colorectal tumors: A mutational "hotspot" and interdependence of the "two hits".
A. J. Rowan, H. Lamlum, M. Ilyas, J. Wheeler, J. Straub, A. Papadopoulou, D. Bicknell, W. F. Bodmer, and I. P. M. Tomlinson (2000)
PNAS 97, 3352-3357
   Abstract »    Full Text »    PDF »
Appendiceal carcinoma complicating adenomatous polyposis in a young woman with a de novo constitutional reciprocal translocation t(5;8)(q22;p23.1).
D KOOREY, N J BASHA, C TOMARAS, J FREIMAN, L ROBSON, and A SMITH (2000)
J. Med. Genet. 37, 71-75
   Full Text »
Localization of MCC (Mutated in Colorectal Cancer) in Various Tissues of Mice and Its Involvement in Cell Differentiation.
T. Senda, A. Matsumine, H. Yanai, and T. Akiyama (1999)
J. Histochem. Cytochem. 47, 1149-1158
   Abstract »    Full Text »
Colorectal Cancer: Molecules and Populations.
J. D. Potter (1999)
J Natl Cancer Inst 91, 916-932
   Abstract »    Full Text »    PDF »
Nuclear endpoint of Wnt signaling: Neoplastic transformation induced by transactivating lymphoid-enhancing factor 1.
M. Aoki, A. Hecht, U. Kruse, R. Kemler, and P. K. Vogt (1999)
PNAS 96, 139-144
   Abstract »    Full Text »    PDF »
Cancer Control in Susceptible Groups: Opportunities and Challenges.
F. P. Li (1999)
J. Clin. Oncol. 17, 719
   Abstract »    Full Text »    PDF »
Novel Members of the Vesl/Homer Family of PDZ Proteins That Bind Metabotropic Glutamate Receptors.
A. Kato, F. Ozawa, Y. Saitoh, Y. Fukazawa, H. Sugiyama, and K. Inokuchi (1998)
J. Biol. Chem. 273, 23969-23975
   Abstract »    Full Text »    PDF »
A contiguous high-resolution radiation hybrid map of 44 loci from the distal portion of the long arm of human chromosome 5..
J A Warrington and J J Wasmuth (1996)
Genome Res. 6, 628-632
   Abstract »    PDF »
MCC, a Cytoplasmic Protein That Blocks Cell Cycle Progression from the G(0)/G(1) to S Phase.
A. Matsumine, T. Senda, G.-H. Baeg, B. C. Roy, Y. Nakamura, M. Noda, K. Toyoshima, and T. Akiyama (1996)
J. Biol. Chem. 271, 10341-10346
   Abstract »    Full Text »    PDF »
Gastrointestinal Polyposis and Nonpolyposis Syndromes.
W. S. Samowitz, R. W. Burt, M. Leppert, M.J.M. Dupuis, C. Verellen-Dumoulin, T. Coyle, M. F. Ellis, S. Whitelaw, and A. K. Rustgi (1995)
N. Engl. J. Med. 332, 1518-1520
   Full Text »
Hereditary Gastrointestinal Polyposis and Nonpolyposis Syndromes.
A. K. Rustgi (1994)
N. Engl. J. Med. 331, 1694-1702
   Full Text »
Cloning of Tumor Suppressor Genes Involved in Solid Tumor Development.
D. I. Smith and M. del Mar Alonso (1993)
Arch Otolaryngol Head Neck Surg 119, 1210-1216
   Abstract »    PDF »
Animal Models for Colon Carcinogenesis.
S. E. Pories, N. Ramchurren, I. Summerhayes, and G. Steele (1993)
Arch Surg 128, 647-653
   Abstract »    PDF »
Molecular Medicine: A Spin-off From the Helix.
C. T. Caskey (1993)
JAMA 269, 1986-1992
   Abstract »    PDF »
Altered growth of human colon cancer cell lines disrupted at activated Ki-ras.
S Shirasawa, M Furuse, N Yokoyama, and T Sasazuki (1993)
Science 260, 85-88
   Abstract »    PDF »
Deletion of IRF-1, mapping to chromosome 5q31.1, in human leukemia and preleukemic myelodysplasia.
C. Willman, C. Sever, M. Pallavicini, H Harada, N Tanaka, M. Slovak, H Yamamoto, K Harada, T. Meeker, A. List, et al. (1993)
Science 259, 968-971
   Abstract »
Multistep carcinogenesis: a 1992 perspective.
T Sugimura (1992)
Science 258, 603-607
   Abstract »    PDF »
Reconciling the Epidemiology, Physiology, and Molecular Biology of Colon Cancer.
J. D. Potter (1992)
JAMA 268, 1573-1577
   Abstract »    PDF »
Multiple intestinal neoplasia caused by a mutation in the murine homolog of the APC gene.
L. Su, K. Kinzler, B Vogelstein, A. Preisinger, A. Moser, C Luongo, K. Gould, and W. Dove (1992)
Science 256, 668-670
   Abstract »    PDF »
Chromosome aberrations and cancer.
E Solomon, J Borrow, and A. Goddard (1991)
Science 254, 1153-1160
   Abstract »    PDF »
Identification of FAP locus genes from chromosome 5q21.
K. Kinzler, M. Nilbert, L. Su, B Vogelstein, T. Bryan, D. Levy, K. Smith, A. Preisinger, P Hedge, D McKechnie, et al. (1991)
Science 253, 661-665
   Abstract »    PDF »
Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients.
I Nishisho, Y Nakamura, Y Miyoshi, Y Miki, H Ando, A Horii, K Koyama, J Utsunomiya, S Baba, and P Hedge (1991)
Science 253, 665-669
   Abstract »    PDF »
Recent advances in the polymerase chain reaction.
H. Erlich, D Gelfand, and J. Sninsky (1991)
Science 252, 1643-1651
   Abstract »    PDF »
Possible new colon cancer gene found.
J Marx (1991)
Science 251, 1317
   PDF »
Phosphorylation near nuclear localization signal regulates nuclear import of adenomatous polyposis coli protein.
F. Zhang, R. L. White, and K. L. Neufeld (2000)
PNAS 97, 12577-12582
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)