Abstract
Juvenile polyposis (JP) is a rare dominantly inherited tumor predisposition syndrome, the typical lesion being a benign hamartomatous intestinal polyp with dilated crypts. Solitary juvenile polyps are relatively common in childhood, and appear not to be associated with neoplasia (1,2). There is no consensus of how many polyps in one patient would justify the diagnosis for the condition. The number of polyps usually present is low compared to familial adenomatous polyposis where typically hundreds of lesions are found in the fully developed disease. Five histologically confirmed juvenile polyps in one patient have been proposed as a sufficient number to establish juvenile polyposis diagnosis (3). Juvenile polyposis usually presents in childhood, most often with rectal bleeding. In some cases associated congenital defects such as malform ations of the heart and the cranium occur (4,5).
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References
Nugent, K. P., Talbot, I. C., Hodgson, S. V., and Phillips, R. K. (1993) Solitary juvenile polyps: not a marker for subsequent malignancy. Gastroenterology 105, 698–700.
Wu, T. T., Rezai, B., Rashid, A., Luce, M. C., Cayouette, M. C., Kim, C., et al. (1997) Genetic alterations and epithelial dysplasia in juvenile polyposis syndrome and sporadic juvenile polyps. Am. J. Pathol. 150, 939–947.
Jass, J. R., Williams, C. B., Bussey, H. J., and Morson, B.C. (1988) Juvenile polyposis-a precancerous condition. Histopathology 13, 619–630.
Phillips, R. K. S., Spigelman, A. D., and Thomson, J. P. S. (eds.) (1994) Familial Adenomatous Polyposis and Other Polyposis Syndromes. Edward Arnold, London, pp. 204,205.
Desai, D. C., Murday, V., Phillips, R. K., Neale, K. F., Milla, P., and Hodgson, S. V. (1998) A survey of phenotypic features in juvenile polyposis. J. Med. Genet. 35, 476–481.
Coburn, M. C., Pricolo, V. E., DeLuca, F. G., and Bland, K. I. (1995) Malignant potential in intestinal juvenile polyposis syndromes. Ann. Surg. Oncol. 2, 386–391.
Sharma, A. K., Sharma, S. S., and Mathur, P. (1995) Familial juvenile polyposis with adenomatous-carcinomatous change. J. Gastroenterol. Hepatol. 10, 131–134.
Howe, J. R., Mitros, F. A., and Summers, R. W. (1998) The risk of gastrointestinal carcinoma in familial juvenile polyposis. Ann. Surg. Oncol. 5, 751–756.
Agnifili, A., Verzaro, R., Gola, P., Marino, M., Mancini, E., Carducci, G., et al. (1999) Juvenile polyposis: case report and assessment of the neoplastic risk in 271 patients reported in the literature. Dig. Surg. 16, 161–166.
Järvinen, H. J., Mecklin, J.-P., and Sistonen, P. (1995) Screening reduces colorectal cancer rate in families with hereditary nonpolyposis colorectal cancer. Gastroenterology 108, 1405–1411.
Olschwang, S., Serova-Sinilnikova, O. M., Lenoir, G., and Thomas, G. (1998) PTEN germline mutations in juvenile polyposis coli. Nature Genet. 18, 12–14.
Marsh, D. J., Roth, S., Lunetta, K. L., Hemminki, A., Dahia, P. L., Sistonen, P., et al. (1997) Exclusion of PTEN and 10q22-24 as the susceptibility locus for juvenile polyposis syndrome. Cancer Res. 57, 5017–5021.
Kurose, K., Araki, T., Matsunaka, T., Takada, Y., and Emi, M. Variant manifestation of Cowden disease in Japan: hamatomatous polyposis of the digestive tract with mutation of the PTEN gene. Am. J. Hum. Genet. 64, 308–310.
Hahn, S. A., Schutte, M., Hoque, A. T., Moskaluk, C. A., da Costa, L. T., Rozenblum, E., et al. (1996) DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1. Science 271, 350–353.
Howe, J. R., Roth, S., Ringold, J. C., Summers, R. W., Järvinen, H. J., Sistonen, P., et al. Mutations in the Smad4/DPC4 gene in juvenile polyposis. Science 280, 1086–1088.
Houlston, R., Bevan, S., Williams, A., Young, J., Dunlop, M., Rozen, P., et al. (1998) Mutations in DPC4 (SMAD4) cause juvenile polyposis syndrome, but only account for a minority of cases. Hum. Mol. Genet. 7, 1907–1912.
Heldin, C. H., Miyazono, K., and ten Dijke, P. (1997) TGF-βeta signalling from cell membrane to nucleus through SMAD proteins. Nature 390, 465–471.
Roth, S., Sistonen, P., Hemminki, A,. Salovaara, R., Loukola, A., Johansson, M., et al. Smad genes in juvenile polyposis. Gene. Chrom. Cancer 26, 54–61.
Takagi, Y., Kohmura, H., Futamura, M., Kida, H., Tanemura, H., Shimokawa, K., and Saji, S. (1996) Somatic alterations of the DPC4 gene in human colorectal cancers in vivo. Gastroenterology 111, 1369–1372.
Miyaki, M., Iijima, T., Konishi, M., Sakai, K., Ishii, A., Yasuno, M., et al. (1999) Higher frequency of Smad4 gene mutation in human colorectal cancer with distant metastasis. Oncogene 18, 3098–3103.
Bartsch, D., Hahn, S. A., Danichevski, K. D., Ramaswamy, A., Bastian, D., Galehdari, H., et al. (1999) Mutations of the DPC4/Smad4 gene in neuroendo-crine pancreatic tumors. Oncogene 18, 2367–2371.
Nagatake, M., Takagi, Y., Osada, H., Uchida, K., Mitsudomi, T., Saji, S., et al. (1996) Somatic in vivo alterations of the DPC4 gene at 18q21 in human lung cancers. Cancer Res. 56, 2718–2720.
Schutte, M., Hruban, R. H., Hedrick, L., Cho, K. R., Nadasdy, G. M., Weinstein, C. L., et al. (1996) DPC4 gene in various tumor types. Cancer Res. 56, 2527–2530.
Kim, S. K., Fan, Y., Papadimitrakopoulou, V., Clayman, G., Hittelman, W. N., Hong, W. K., et al. (1996) DPC4, a candidate tumor suppressor gene, is altered infrequently in head and neck squamous cell carcinoma. Cancer Res. 56, 2519–2521.
Zhou, Y., Kato, H., Shan, D., Minami, R., Kitazawa, S., Matsuda, T., et al. (1999) Involvement of mutations in the DPC4 promoter in endometrial carcinoma development. Mol. Carcinog. 25, 64–72.
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Aaltonen, L.A., Roth, S. (2001). Direct Sequencing for Juvenile Polyposis Gene SMAD4/DPC4 Mutations. In: M., S. (eds) Colorectal Cancer. Methods in Molecular Medicine, vol 50. Humana Press. https://doi.org/10.1385/1-59259-084-5:167
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DOI: https://doi.org/10.1385/1-59259-084-5:167
Publisher Name: Humana Press
Print ISBN: 978-0-89603-767-0
Online ISBN: 978-1-59259-084-1
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