Mutations in the SMAD4/DPC4 gene in juvenile polyposis

Science

Volumn 280, Issue 5366, 1998, Pages 1086-1088

  Howe, James R ^a   Roth, Stina ^b   Ringold, John C ^a   Summers, Robert W ^a   Järvinen, Heikki J ^c   Sistonen, Pertti ^d   Tomlinson, Ian P M ^e   Houlston, Richard S ^f   Bevan, Steve ^f   Mitros, Frank A ^a   Stone, Edwin M ^a   Aaltonen, Lauri A ^b  

^a UNIVERSITY OF IOWA   (United States)

^b UNIVERSITY OF HELSINKI   (Finland)

^c HELSINKI UNIVERSITY CENTRAL HOSPITAL   (Finland)

^d FINNISH RED CROSS BLOOD SERVICE   (Finland)

^e IMPERIAL CANCER RESEARCH FUND   (United Kingdom)

^f INSTITUTE OF CANCER RESEARCH   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

TRANSFORMING GROWTH FACTOR BETA;

ARTICLE; AUTOSOMAL DOMINANT DISORDER; CARBOXY TERMINAL SEQUENCE; CHROMOSOME 18Q; DIGESTIVE SYSTEM CANCER; DISEASE PREDISPOSITION; GENE ISOLATION; GENE MAPPING; GENE MUTATION; HUMAN; HUMAN CELL; HUMAN TISSUE; JUVENILE POLYP; PRIORITY JOURNAL;

CELL MEMBRANE; CELL NUCLEUS; CHROMOSOME MAPPING; CHROMOSOMES, HUMAN, PAIR 18; COLORECTAL NEOPLASMS; DNA-BINDING PROTEINS; FEMALE; FRAMESHIFT MUTATION; GASTROINTESTINAL NEOPLASMS; GENES, DCC; GENES, TUMOR SUPPRESSOR; GENETIC PREDISPOSITION TO DISEASE; GERM-LINE MUTATION; HAMARTOMA SYNDROME, MULTIPLE; HUMANS; INTESTINAL POLYPS; MALE; PEDIGREE; POLYMERASE CHAIN REACTION; SEQUENCE DELETION; SIGNAL TRANSDUCTION; SMAD4 PROTEIN; TRANS-ACTIVATORS; TRANSFORMING GROWTH FACTOR BETA;

EID: 0032524069     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.280.5366.1086     Document Type: Article

References (34)

1. H. J. Järvinen and K. O. Franssila, Gut 25, 792 (1984); J. R. Jass, in Familial Adenomatous Polyposis and Other Polyposis Syndromes, R. K. S. Phillips, A. D. Spigelman, J. P. S, Thomson, Eds. (Edward Arnold, London, 1994), pp. 203-214 ; J. R. Howe, F. A. Mitros, R. W. Summers, in preparation. Estimates of gastrointestinal cancer vary widely because there have been few studies in large families with long-term follow-up.
2. H. J. Järvinen and K. O. Franssila, Gut 25, 792 (1984); J. R. Jass, in Familial Adenomatous Polyposis and Other Polyposis Syndromes, R. K. S. Phillips, A. D. Spigelman, J. P. S, Thomson, Eds. (Edward Arnold, London, 1994), pp. 203-214 ; J. R. Howe, F. A. Mitros, R. W. Summers, in preparation. Estimates of gastrointestinal cancer vary widely because there have been few studies in large families with long-term follow-up.
3. H. J. Järvinen and K. O. Franssila, Gut 25, 792 (1984); J. R. Jass, in Familial Adenomatous Polyposis and Other Polyposis Syndromes, R. K. S. Phillips, A. D. Spigelman, J. P. S, Thomson, Eds. (Edward Arnold, London, 1994), pp. 203-214 ; J. R. Howe, F. A. Mitros, R. W. Summers, in preparation. Estimates of gastrointestinal cancer vary widely because there have been few studies in large families with long-term follow-up.
4. E. D. Lynch et al., Am. J. Hum. Genet. 61, 1254 (1997); S. Olschwang et al., Nature Genet. 18, 12 (1998).
5. E. D. Lynch et al., Am. J. Hum. Genet. 61, 1254 (1997); S. Olschwang et al., Nature Genet. 18, 12 (1998).
6. D. Liaw et al., Nature Genet. 16, 64 (1997); D. J. Marsh et al., ibid., p. 333.
7. D. Liaw et al., Nature Genet. 16, 64 (1997); D. J. Marsh et al., ibid., p. 333.
8. D. J. Marsh et al., Cancer Res. 57, 5017 (1997); G. J. Riggins, S. R. Hamilton, K. W. Kinzler, B. Vogelstein, "Normal PTEN Gene in Juvenile Polyposis," J. Neg. Obs. Gen. Oncol. [online] 1, 1 (1997). Available at http://128.220.85.41:5002/NOGO.
9. D. J. Marsh et al., Cancer Res. 57, 5017 (1997); G. J. Riggins, S. R. Hamilton, K. W. Kinzler, B. Vogelstein, "Normal PTEN Gene in Juvenile Polyposis," J. Neg. Obs. Gen. Oncol. [online] 1, 1 (1997). Available at http://128.220.85.41:5002/NOGO.
10. C. Eng and H. Ji, Am. J. Hum. Genet. 62, 1020 (1998).
11. J. R. Howe et al., ibid., p. 1129.
12. K. Eppert et al., Cell 86, 543 (1996).
13. T. J. Stemper, T. H. Kent, R. W. Summers, Ann. Int. Med. 83, 639 (1975).
14. K. R. Cho et al., Genomics 19, 525 (1994).
15. 2, 0.01% w/v gelatin], 2 pmol of each primer, and 0.25 units of Taq DNA polymerase. PCR was performed for 1 min at 94°C, 1 min at 55°C (or optimal annealing temperature), and 1 min at 72°C for 30 cycles. After amplification, 5 μI of stop solution (95% formamide, 10 mM NaOH, 0.05% bromophenol blue, 0.05% xylene cyanol) was added, and samples were heated to 95°C for 3 min, then loaded onto 6% nondenaturing polyacrylamide gels (with and without 10% glycerol). DNA was detected by silver staining. Informed consent for DNA studies was obtained from family members with the approval of the Institutional Review Board at the University of Iowa.
16. PCR products were subjected to electrophoresis through 2% agarose gels and stained with ethidium bromide to confirm the presence of a single band of the expected size. The products were isolated with the Qiaquick PCR purification kit (Qiagen, Santa Clarita, CA) and then sequenced with the ABI Prism Dye Terminator Cycle Sequencing kit (PE Applied Biosystems, Foster City, CA). Cycle sequencing included 1 cycle at 98°C for 5 min, followed by 30 cycles at 94°C for 10 s, 50°C for 5 s, and 60°C for 4 min. Individual PCR primers were used for sequencing the sense and antisense strands for each exon. Reactions were analyzed with an ABI model 373XL stretch fluorescent automated sequencer.
17. Exon 9 was PCR amplified and the gel products purified and ligated into the p-GEM-T Easy plasmid vector (Promega). JM109 cells were transformed with the vector and plated onto LB-ampicillin plates containing 0.5 mM isopropylthio-β-D-galactoside and 5-bromo-4-chloro-3-indolyl-β-D-galactoside (80 μg/ml). Recombinant clones were grown overnight at 37°C in LB-ampicillin (100 μg/ml) medium. Cells were harvested and lysed, and cycle sequencing was performed with DPC4S9 and AS9 primers.
18. S. A. Hahn et al., Science 271, 350 (1996).
19. M. Schutte et al., Cancer Res. 56, 2527 (1996).
20. S. Thiagalingam et al., Nature Genet. 13, 343 (1996).
21. J. L. Wrana and L. Attisano, Trends Genet. 12, 493 (1996).
22. G. Lagna et al., Nature 383, 832 (1996).
23. J. Wrana and T. Pawson, ibid. 388, 28 (1997).
24. A. M. Grau et al., Cancer Res. 57, 3929 (1997).
25. Y. Shi et al., Nature 388, 87 (1997).
26. Y. Takagi et al., Gastroenterology 111, 1369 (1996).
27. S. K. Kim et al., Cancer Res. 56, 2519 (1996).
28. K. Takaku et al., Cell 92, 645 (1998).
29. L. A. Aaltonen, R. S. Houlston, S. Bevan, I. P. M. Tomlinson, unpublished data.
30. A. Hemminki et al., Nature 391, 184 (1998).
31. D.-M. Li and H. Sun, Cancer Res. 57, 2124 (1997).
32. C. A. Moskaluk et al., Diagn. Mol. Pathol. 6, 85 (1997).
33. J. R. Howe, D. S. Klimstra, C. Cordon-Cardo, Histol. Histopathol. 12, 595 (1997).
34. We thank A. Hemminki, P. Kristo, A. Loukola, E. Avizienyte, R. Salovaara, K. Saastamoinen, S. Lindh, T. Lehtinen, and T. Kosonen for assistance. Supported in part by the Owen H. Wangensteen Faculty Research Fellowship of the American College of Surgeons, the Carver Trust Medical Research Initiative Grant, the Clinical Cancer Center at the University of Iowa, the Academy of Finland, the Helsinki University Central Hospital, the Finnish Cancer Society, the Research and Science Foundation of Farmos, the European Commission, the Sigrid Juselius Foundation, and the Coeliac Disease Society.