© 1992 Oxford University Press
RESEARCH-ARTICLE |
Somatic mutations of the APC gene in colorectal tumors: mutation cluster region in the APC gene
1Department of Biochemistry, Cancer Institute 1-37-1, Kami-ikebukuro, Toshima-ku, Tokyo 170 2Second Department of Surgery, Osaka University Medical School 1-1-50, Fukushima, Fukushima-ku, Osaka 553, Japan
*To whom correspondence should be addressed
Received June 1, 1992; Revised June 30, 1992; Accepted June 30, 1992
We examined somatic mutations of the adenomatous polyposis coil (APC) gene in 63 colorectal tumors (16 adenomas and 47 carcinomas) developed in familial adenomatous polyposis (FAP) and non-FAP patients. In addition to loss of heterozygosity (LOH) at the APC locus in 30 tumors, 43 other somatic mutations were detected. Twenty-one of them were point mutations; 16 nonsense and two missense mutations, and three occurred in introns at the splicing site. Twenty-two tumors had frameshift mutations due to deletion or insertion; nineteen of them were deletions of one to 31 bp and three were a 1-bp insertion. One tumor had a 1-bp deletion in an intron near the splicing site. Hence, 41 (95%) of 43 mutations resulted in truncation of the APC protein. Over 60% of the somatic mutations in the APC gene were clustered within a small region of exon 15, designated as MCR (mutation cluster region), which accounted for less than 10% of the coding region. Combining these data and the results of LOH, more than 80% of tumors (14 adenomas and 39 carcinomas) had at least one mutation in the APC gene, of which more than 60% (9 adenomas and 23 carcinomas) had two mutations. These results strongly suggest that somatic mutations of the APC gene are associated with development of a great majority of colorectal tumors.
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J. Erik Paulsen, I.-L. Steffensen, E. M. Loberg, T. Husoy, E. Namork, and J. Alexander Qualitative and Quantitative Relationship between Dysplastic Aberrant Crypt Foci and Tumorigenesis in the Min/+ Mouse Colon Cancer Res., July 1, 2001; 61(13): 5010 - 5015. [Abstract] [Full Text] [PDF]
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A. K. Virmani, A. Rathi, U. G. Sathyanarayana, A. Padar, C. X. Huang, H. T. Cunnigham, A. J. Farinas, S. Milchgrub, D. M. Euhus, M. Gilcrease, et al. Aberrant Methylation of the Adenomatous Polyposis Coli (APC) Gene Promoter 1A in Breast and Lung Carcinomas Clin. Cancer Res., July 1, 2001; 7(7): 1998 - 2004. [Abstract] [Full Text] [PDF]
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N. S. Fearnhead, M. P. Britton, and W. F. Bodmer The ABC of APC Hum. Mol. Genet., April 1, 2001; 10(7): 721 - 733. [Abstract] [Full Text] [PDF]
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P. Peltomaki Deficient DNA mismatch repair: a common etiologic factor for colon cancer Hum. Mol. Genet., April 1, 2001; 10(7): 735 - 740. [Abstract] [Full Text] [PDF]
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H. Takayasu, H. Horie, E. Hiyama, T. Matsunaga, Y. Hayashi, Y. Watanabe, S. Suita, M. Kaneko, F. Sasaki, K. Hashizume, et al. Frequent Deletions and Mutations of the {beta}-Catenin Gene Are Associated with Overexpression of Cyclin D1 and Fibronectin and Poorly Differentiated Histology in Childhood Hepatoblastoma Clin. Cancer Res., April 1, 2001; 7(4): 901 - 908. [Abstract] [Full Text]
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R. A. Wagenaar, H. C. Crawford, and L. M. Matrisian Stabilized {beta}-Catenin Immortalizes Colonic Epithelial Cells Cancer Res., March 1, 2001; 61(5): 2097 - 2104. [Abstract] [Full Text]
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Y. Naishiro, T. Yamada, A. S. Takaoka, R. Hayashi, F. Hasegawa, K. Imai, and S. Hirohashi Restoration of Epithelial Cell Polarity in a Colorectal Cancer Cell Line by Suppression of {beta}-catenin/T-Cell Factor 4-mediated Gene Transactivation Cancer Res., March 1, 2001; 61(6): 2751 - 2758. [Abstract] [Full Text]
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I.-M. Shih, T.-L. Wang, G. Traverso, K. Romans, S. R. Hamilton, S. Ben-Sasson, K. W. Kinzler, and B. Vogelstein Top-down morphogenesis of colorectal tumors PNAS, February 15, 2001; (2001) 51629398. [Abstract] [Full Text]
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 A. Reinacher-Schick and B. M. Gumbiner Apical Membrane Localization of the Adenomatous Polyposis Coli Tumor Suppressor Protein and Subcellular Distribution of the {beta}-Catenin Destruction Complex in Polarized Epithelial Cells J. Cell Biol., February 5, 2001; 152(3): 491 - 502. [Abstract] [Full Text] [PDF]
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I P M Tomlinson, R Roylance, and R S Houlston Two hits revisited again J. Med. Genet., February 1, 2001; 38(2): 81 - 85. [Abstract] [Full Text]
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M M Entius, J J Keller, A M Westerman, B P van Rees, M-L F van Velthuysen, A F P M de Goeij, J H P Wilson, F M Giardiello, and G J A Offerhaus Molecular genetic alterations in hamartomatous polyps and carcinomas of patients with Peutz-Jeghers syndrome J. Clin. Pathol., February 1, 2001; 54(2): 126 - 131. [Abstract] [Full Text] [PDF]
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L. T. Ziemer, D. Pennica, and A. J. Levine Identification of a Mouse Homolog of the Human BTEB2 Transcription Factor as a {beta}-Catenin-Independent Wnt-1-Responsive Gene Mol. Cell. Biol., January 15, 2001; 21(2): 562 - 574. [Abstract] [Full Text]
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R HOULSTON, M CRABTREE, R PHILLIPS, M CRABTREE, and I TOMLINSON Explaining differences in the severity of familial adenomatous polyposis and the search for modifier genes Gut, January 1, 2001; 48(1): 1 - 5. [Full Text] [PDF]
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T. Tsujiuchi, M. Tsutsumi, Y. Sasaki, N. Murata, and Y. Konishi Mutations of Adenomatous Polyposis Coli and {beta}-Catenin Genes during Progression of Lung Tumors Induced by N-Nitrosobis(2-hydroxypropyl)amine in Rats Cancer Res., December 1, 2000; 60(23): 6611 - 6616. [Abstract] [Full Text]
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M. Miyaki, T. Iijima, R. Ishii, T. Hishima, T. Mori, K. Yoshinaga, H. Takami, T. Kuroki, and T. Iwama Molecular Evidence for Multicentric Development of Thyroid Carcinomas in Patients with Familial Adenomatous Polyposis Am. J. Pathol., December 1, 2000; 157(6): 1825 - 1827. [Abstract] [Full Text] [PDF]
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M. Iwamoto, D. J Ahnen, W. A. Franklin, and T. H. Maltzman Expression of {beta}-catenin and full-length APC protein in normal and neoplastic colonic tissues Carcinogenesis, November 1, 2000; 21(11): 1935 - 1940. [Abstract] [Full Text] [PDF]
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M. B. H. Petrik, M. F. McEntee, B. T. Johnson, M. G. Obukowicz, and J. Whelan Highly Unsaturated (n-3) Fatty Acids, but Not {alpha}-Linolenic, Conjugated Linoleic or {gamma}-Linolenic Acids, Reduce Tumorigenesis in ApcMin/+ Mice J. Nutr., October 1, 2000; 130(10): 2434 - 2443. [Abstract] [Full Text]
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 J. Z. Chen, J. Qiu, B. Shen, and G. P. Holmquist Mutational spectrum analysis of RNase H(35) deficient Saccharomyces cerevisiae using fluorescence-based directed termination PCR Nucleic Acids Res., September 15, 2000; 28(18): 3649 - 3656. [Abstract] [Full Text] [PDF]
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H. Lamlum, N. Al Tassan, E. Jaeger, I. Frayling, O. Sieber, F. B. Reza, M. Eckert, A. Rowan, E. Barclay, W. Atkin, et al. Germline APC variants in patients with multiple colorectal adenomas, with evidence for the particular importance of E1317Q Hum. Mol. Genet., September 1, 2000; 9(15): 2215 - 2221. [Abstract] [Full Text] [PDF]
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K. Shailubhai, H. H. Yu, K. Karunanandaa, J. Y. Wang, S. L. Eber, Y. Wang, N. S. Joo, H. D. Kim, B. W. Miedema, S. Z. Abbas, et al. Uroguanylin Treatment Suppresses Polyp Formation in the ApcMin/+ Mouse and Induces Apoptosis in Human Colon Adenocarcinoma Cells via Cyclic GMP Cancer Res., September 1, 2000; 60(18): 5151 - 5157. [Abstract] [Full Text]
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M. Esteller, A. Sparks, M. Toyota, M. Sanchez-Cespedes, G. Capella, M. A. Peinado, S. Gonzalez, G. Tarafa, D. Sidransky, S. J. Meltzer, et al. Analysis of Adenomatous Polyposis Coli Promoter Hypermethylation in Human Cancer Cancer Res., August 1, 2000; 60(16): 4366 - 4371. [Abstract] [Full Text]
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P. W. Schlosshauer, S. A. Brown, K. Eisinger, Q. Yan, E. R. Guglielminetti, R. Parsons, L. H. Ellenson, and J. Kitajewski APC truncation and increased {beta}-catenin levels in a human breast cancer cell line Carcinogenesis, July 1, 2000; 21(7): 1453 - 1456. [Abstract] [Full Text] [PDF]
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Y. Yamada, N. Yoshimi, Y. Hirose, K. Kawabata, K. Matsunaga, M. Shimizu, A. Hara, and H. Mori Frequent {beta}-Catenin Gene Mutations and Accumulations of the Protein in the Putative Preneoplastic Lesions Lacking Macroscopic Aberrant Crypt Foci Appearance, in Rat Colon Carcinogenesis Cancer Res., July 1, 2000; 60(13): 3323 - 3327. [Abstract] [Full Text]
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W. J. Thompson, G. A. Piazza, H. Li, L. Liu, J. Fetter, B. Zhu, G. Sperl, D. Ahnen, and R. Pamukcu Exisulind Induction of Apoptosis Involves Guanosine 3',5'-Cyclic Monophosphate Phosphodiesterase Inhibition, Protein Kinase G Activation, and Attenuated {beta}-Catenin Cancer Res., July 1, 2000; 60(13): 3338 - 3342. [Abstract] [Full Text]
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K. Furuuchi, M. Tada, H. Yamada, A. Kataoka, N. Furuuchi, J.-i. Hamada, M. Takahashi, S. Todo, and T. Moriuchi Somatic Mutations of the APC Gene in Primary Breast Cancers Am. J. Pathol., June 1, 2000; 156(6): 1997 - 2005. [Abstract] [Full Text] [PDF]
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K. H. Goss and J. Groden Biology of the Adenomatous Polyposis Coli Tumor Suppressor J. Clin. Oncol., May 9, 2000; 18(9): 1967 - 1979. [Abstract] [Full Text] [PDF]
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M. B. H. Petrik, M. F. McEntee, C.-H. Chiu, and J. Whelan Antagonism of Arachidonic Acid Is Linked to the Antitumorigenic Effect of Dietary Eicosapentaenoic Acid in ApcMin/+ Mice J. Nutr., May 1, 2000; 130(5): 1153 - 1158. [Abstract] [Full Text]
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A. J. Rowan, H. Lamlum, M. Ilyas, J. Wheeler, J. Straub, A. Papadopoulou, D. Bicknell, W. F. Bodmer, and I. P. M. Tomlinson APC mutations in sporadic colorectal tumors: A mutational "hotspot" and interdependence of the "two hits" PNAS, March 28, 2000; 97(7): 3352 - 3357. [Abstract] [Full Text] [PDF]
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K. Kawahara, T. Morishita, T. Nakamura, F. Hamada, K. Toyoshima, and T. Akiyama Down-regulation of beta -Catenin by the Colorectal Tumor Suppressor APC Requires Association with Axin and beta -Catenin J. Biol. Chem., March 17, 2000; 275(12): 8369 - 8374. [Abstract] [Full Text] [PDF]
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M. Enomoto, M. Konishi, T. Iwama, J. Utsunomiya, K.-i. Sugihara, and M. Miyaki The Relationship Between Frequencies of Extracolonic Manifestations and the Position of APC Germline Mutation in Patients with Familial Adenomatous Polyposis Jpn. J. Clin. Oncol., February 1, 2000; 30(2): 82 - 88. [Abstract] [Full Text] [PDF]
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