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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1997 Aug;88(8):718–724. doi: 10.1111/j.1349-7006.1997.tb00442.x

Analyses of the APC and TGF‐β Type II Receptor Genes, and Microsatellite Instability in Mucosal Colorectal Carcinomas

Osmar Kenji Yagi 1, Yoshimitsu Akiyama 2, Yasuo Ohkura 3, Shin‐ichi Ban 4, Mitsuo Endo 1, Kiyoshi Saitoh 5, Yasuhito Yuasa 2,✉
PMCID: PMC5921495  PMID: 9330602

Abstract

APC and transforming growth factor‐β type II receptor (TGF‐β RII) gene mutations, and microsatcllitc instability have been found in sporadic colorectal carcinomas. To clarify further the early alterations in colorectal carcinogenesis, we investigated these genetic changes in 23 protruding‐ and 24 superficial‐type mucosal colorectal carcinomas. TGF‐β RII gene mutations and microsatellite instability were rarely found in these lesions. Nevertheless, APC was mutated in 16 of the 47 (34.0%) mucosal colorectal carcinomas and was significantly more frequently mutated in protruding‐ (I) and superficial elevated‐type (Ila) (14/32,43.8%) than in other superficial‐type (IIa+IIc, IIb, IIc, and IIc+IIa) (2/ 15,13.3%) mucosal colorectal carcinomas (P<0.04). These results indicate that the APC gene may be involved from the beginning in the tumorigenesis of many early colorectal carcinomas, particularly of the protruding and superficial elevated types. However, there might be a distinct pathway for other superficial‐type colorectal carcinomas, possibly not involving APC as an initial step of tumorigenesis.

Keywords: Early colorectal carcinoma, APC, Microsatellite instability, Transforming growth factor‐β type II receptor gene, K‐ras

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REFERENCES

  • 1. ) Morson , B. C.Precancerous and early malignant lesions of the large intestine . Br. J. Surg. , 55 , 725 – 731 ( 1968. ). [DOI] [PubMed] [Google Scholar]
  • 2. ) Vogelstein , B. , Fearon , E. R. , Hamilton , S. R. , Kern , S. E. , Preisinger , A. C. , Leppert , M. , Nakamura , Y. , White , R. , Smits , A. M. M. and Bos , J. L.Genetic alterations during colorectal‐tumor development . N. Engl. J, Med. , 319 , 525 – 532 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 3. ) Kinzler , K. W. and Vogelstein , B.Lessons from hereditary colorectal cancer . Cell , 87 , 159 – 170 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 4. ) Ando , M. , Takemura , K. , Maruyama , M. , Endo , M. , Iwama , T. and Yuasa , Y.Mutations in c‐K‐ras 2 gene codon 12 during colorectal tumorigenesis in familial ad‐enomatous polyposis . Gastroenterology , 103 , 1725 – 1731 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 5. ) Hasegawa , H. , Ueda , M. , Watanabe , M. , Teraraoto , T. , Mukai , M. and Kitajima , M.K‐ras gene mutations in early colorectal cancer…flat elevated vs. polyp‐forming cancer… . Oncogene , 10 , 1413 – 1416 ( 1995. ). [PubMed] [Google Scholar]
  • 6. ) Miyoshi , Y. , Nagase , H. , Ando , H. , Horii , A. , Ichii , S. , Nakatsuru , S. , Aoki , T. , Mild , Y. , Mori , T. and Nakamura , Y.Somatic mutations of the APC gene in colorectal tumors; mutation cluster region in the APC gene . Hum. Mol. Genet. , 1 , 229 – 233 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 7. ) Powell , S. M. , Zilz , N. , Beazer‐Barclay , Y. , Bryan , T. M. , Hamilton , S. R. , Thibodeau , S. N. , Vogelstein , B. and Kinzler , K. W.APC mutations occur early during colorectal tumorigenesis . Nature , 359 , 235 – 237 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 8. ) Su , L.‐K. , Burrel , M. , Hill , D. E. , Qyuris , J. , Brent , R. , Wiltshire , R. , Trent , J. , Vogelstein , B. and Kinzler , K. W.APC binds to the novel protein EB1 . Cancer Res. , 55 , 2972 – 2977 ( 1995. ). [PubMed] [Google Scholar]
  • 9. ) Matsumine , A. , Ogai , A. , Senda , T. , Okumura , N. , Satoh , K. , Baeg , G.‐H. , Kawahara , T. , Kobayashi , S. , Okada , M. , Toyoshima , K. and Akiyama , T.Binding of APC to the human homolog of the Drosophila discs large tumor suppressor protein . Science , 272 , 1020 – 1023 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 10. ) Rubinfeld , B. , Albert , I. , Porfiri , E. , Fiol , C. , Munemitsu , S. and Polakis , P.Binding of GSK3β to the APC‐β‐catenin complex and regulation of complex assembly . Science , 272 , 1023 – 1025 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 11. ) Japanese Research Society for Cancer of the Colon and Rectum . General rules for clinical and pathological studies on cancer of the colon, rectum and anus . Jpn. J. Surg. , 13 , 557 – 598 ( 1983. ). [DOI] [PubMed] [Google Scholar]
  • 12. ) Shimoda , T. , Ikegami , M. , Fujisaki , J. , Matsui , T. , Aizawa , S. and Ishikawa , E.Early colorectal carcinoma with special reference to its development de novo . Cancer , 64 , 1138 – 1146 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 13. ) Kuramoto , S. and Oohara , T.Flat early cancers of the large intestine . Cancer , 64 , 950 – 955 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 14. ) Aoki , T. , Takeda , S. , Yanagisawa , A. , Kato , Y. , Ajioka , Y. , Watanabe , H. , Kudo , S. and Nakamura , Y.APC and p53 mutations in de novo colorectal adenocarcinomas . Hum. Mutat. , 3 , 342 – 346 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 15. ) Wang , J. , Sun , L. , Myeroff , L. , Wang , X. , Gentry , L. E. , Yang , J. , Liang , J. , Zborowska , E. , Markowitz , S. , Willson , J. K. V. and Brattain , M. G.Demonstration that mutation of the type II transforming growth factor β receptor inactivates its tumor suppressor activity in replication error‐positive colon carcinoma cells . J. Biol. Chem. , 270 , 22044 – 22049 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 16. ) Markowitz , S. , Wang , J. , Myeroff , L. , Parsons , R. , Sun , L. , Lutterbaugh , J. , Fan , R. S. , Zborowska , E. , Kinzler , K. W. , Vogelstein , B. , Brattain , M. and Wilson , J. K. V.Inactivation of the type II TGF‐β receptor in colon cancer cells with microsatellite instability . Science , 268 , 1336 – 1338 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 17. ) Lu , S.‐L. , Akiyama , Y. , Nagasaki , H. , Saitoh , K. and Yuasa , Y.Mutations of the transforming growth factor‐β type II receptor gene and genomic instability in hereditary nonpolyposis colorectal cancer . Biochem. Biophys. Res. Commun. , 216 , 452 – 457 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 18. ) Myeroff , L. L. , Parsons , R. , Kim , S.‐J. , Hedrick , L. , Cho , K. R. , Orth , K. , Mathis , M. , Kinzler , K. W. , Lutterbaugh , J. , Park , K. , Bang , Y.‐J. , Lee , H. Y. , Park , J.‐G. , Lynch , H. T. , Roberts , A. B. , Vogelstein , B. and Markowitz , S. D.A transforming growth factor β receptor type II gene mutation common in colon and gastric but rare in endometrial cancers with microsatellite instability . Cancer Res. , 55 , 5545 – 5547 ( 1995. ). [PubMed] [Google Scholar]
  • 19. ) Parsons , R. , Myeroff , L. L. , Liu , B. , Willson , J. K. V. , Markowitz , S. D. , Kinzler , K. W. and Vogelstein , B.Microsatellite instability and mutations of the transforming growth factor β type II receptor gene in colorectal cancer . Cancer Res. , 55 , 5548 – 5550 ( 1995. ). [PubMed] [Google Scholar]
  • 20. ) Akiyama , Y. , Iwanaga , R. , Saitoh , K. , Shiba , K. , Ushio , K. , Ikeda , E. , Iwama , T. , Nomizu , T. and Yuasa , Y.Transforming growth factor β type II receptor gene in adenomas from hereditary nonpolyposis colorectal cancer . Gastroenterology , 112 , 33 – 39 ( 1997. ). [DOI] [PubMed] [Google Scholar]
  • 21. ) Akiyama , Y. , Iwanaga , R. , Ishikawa , T. , Sakamoto , K. , Nishi , N‐ , Nihei , Z. , Iwama , T. , Saitoh , K. and Yuasa , Y.Mutations of the transforming growth factor‐β type II receptor gene are strongly related to sporadic proximal colon carcinomas with microsatellite instability . Cancer , 78 , 2478 – 2484 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 22. ) Goelz , S. E. , Hamilton , S. R. and Vogelstein , B.Purification of DNA from formaldehyde fixed and paraffin embedded human tissue . Biochem. Biophys. Res. Commun. , 130 , 118 – 126 ( 1985. ). [DOI] [PubMed] [Google Scholar]
  • 23. ) Aaltonen , L. A. , Peltomäki , P. , Leach , F. S. , Sistonen , P. , Pylkkänen , L. , Mecklin , J.‐P. , Järvinen , H. , Powell , S. M. , Jen , J. , Hamilton , S. R. , Petersen , G. M. , Kinzler , K. W. , Vogelstein , B. and de la Chapelle , A.Clues to the patho‐genesis of familial colorectal cancer . Science , 260 , 812 – 816 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 24. ) Hemminki , A. , Peltomäki , P. , Mecklin , J.‐P. , Järvinen , H. , Salovaara , R. , Nyström‐Lahti , M. , de la Chapelle , A. and Aaltoneen , L. A.Loss of the wild type MLHI gene is a feature of hereditary nonpolyposis colorectal cancer . Nat. Genet. , 8 , 405 – 410 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 25. ) Oto , M. , Miyake , S. and Yuasa , Y.Optimization of nonradioisotopic single strand conformation polymorphism analysis with a conventional minislab gel electro‐phoresis apparatus . Anal Biochem. , 213 , 19 – 22 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 26. ) Béroud , C. and Soussi , T.APC gene: database of germline and somatic mutations in human tumors and cell lines . Nucleic Acids Res. , 24 , 121 – 124 ( 1996. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27. ) Haliassos , A. , Chomel , J. C. , Grandjouan , S. , Kruh , J. , Kaplan , J. C. and Kitzis , A.Detection of minority point mutations by modified PCR technique: a new approach for a sensitive diagnosis of tumor‐progression markers . Nucleic Acids Res. , 17 , 8093 – 8099 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28. ) Kudo , S. , Tamura , S. , Hirota , S. , Sano , Y. , Yamano , H. , Serizawa , M. , Fukuoka , T. , Mitsuoka , H. , Nakajima , T. and Kusaka , H.The problem of de novo colorectal carcinoma . Eur. J. Cancer , 31A , 1118 – 1120 ( 1995. ). [DOI] [PubMed] [Google Scholar]

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