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Science 19 January 1996:
Vol. 271. no. 5247, pp. 350 - 353
DOI: 10.1126/science.271.5247.350
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Reports

DPC4, A Candidate Tumor Suppressor Gene at Human Chromosome 18q21.1

Stephan A. Hahn,  Mieke Schutte,  A. T. M. Shamsul Hoque,  Christopher A. Moskaluk,  Luis T. da Costa,  Ester Rozenblum,  Craig L. Weinstein,  Aryeh Fischer,  Charles J. Yeo,  Ralph H. Hruban,  Scott E. Kern (1)

About 90 percent of human pancreatic carcinomas show allelic loss at chromosome 18q. To identify candidate tumor suppressor genes on 18q, a panel of pancreatic carcinomas were analyzed for convergent sites of homozygous deletion. Twenty-five of 84 tumors had homozygous deletions at 18q21.1, a site that excludes DCC (a candidate suppressor gene for colorectal cancer) and includes DPC4, a gene similar in sequence to a Drosophila melanogaster gene (Mad) implicated in a transforming growth factor-beta (TGF-beta)-like signaling pathway. Potentially inactivating mutations in DPC4 were identified in six of 27 pancreatic carcinomas that did not have homozygous deletions at 18q21.1. These results identify DPC4 as a candidate tumor suppressor gene whose inactivation may play a role in pancreatic and possibly other human cancers.


S. A. Hahn, M. Schutte, A. T. M. S. Hoque, C. A. Moskaluk, E. Rozenblum, C. L. Weinstein, A. Fischer, R. H. Hruban, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
L. T. da Costa, Graduate Program in Human Genetics and Molecular Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
C. J. Yeo, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
S. E. Kern, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
(1) To whom correspondence should be addressed.


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   Abstract »    Full Text »    PDF »
Acceleration of Smad2 and Smad3 Phosphorylation via c-Jun NH2-Terminal Kinase during Human Colorectal Carcinogenesis.
H. Yamagata, K. Matsuzaki, S. Mori, K. Yoshida, Y. Tahashi, F. Furukawa, G. Sekimoto, T. Watanabe, Y. Uemura, N. Sakaida, et al. (2005)
Cancer Res. 65, 157-165
   Abstract »    Full Text »    PDF »
Regulation of gonadotropin subunit gene transcription.
L L Burger, D J Haisenleder, A C Dalkin, and J C Marshall (2004)
J. Mol. Endocrinol. 33, 559-584
   Abstract »    Full Text »    PDF »
Use of microsatellite marker loss of heterozygosity in accurate diagnosis of pancreaticobiliary malignancy from brush cytology samples.
A Khalid, R Pal, E Sasatomi, P Swalsky, A Slivka, D Whitcomb, and S Finkelstein (2004)
Gut 53, 1860-1865
   Abstract »    Full Text »    PDF »
Autocrine Motility Factor Signaling Enhances Pancreatic Cancer Metastasis.
S. Tsutsumi, T. Yanagawa, T. Shimura, H. Kuwano, and A. Raz (2004)
Clin. Cancer Res. 10, 7775-7784
   Abstract »    Full Text »    PDF »
THE ROLE OF TGF-{beta} IN EPITHELIAL MALIGNANCY AND ITS RELEVANCE TO THE PATHOGENESIS OF ORAL CANCER (PART II).
S.S. Prime, M. Davies, M. Pring, and I.C. Paterson (2004)
Critical Reviews in Oral Biology & Medicine 15, 337-347
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Activin Type II Receptor Restoration in ACVR2-Deficient Colon Cancer Cells Induces Transforming Growth Factor-{beta} Response Pathway Genes.
E. Deacu, Y. Mori, F. Sato, J. Yin, A. Olaru, A. Sterian, Y. Xu, S. Wang, K. Schulmann, A. Berki, et al. (2004)
Cancer Res. 64, 7690-7696
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Restoration of receptor-type protein tyrosine phosphatase {eta} function inhibits human pancreatic carcinoma cell growth in vitro and in vivo.
F. Trapasso, S. Yendamuri, K. R. Dumon, R. Iuliano, R. Cesari, B. Feig, R. Seto, L. Infante, H. Ishii, A. Vecchione, et al. (2004)
Carcinogenesis 25, 2107-2114
   Abstract »    Full Text »    PDF »
Differential Activation of Smads in HeLa and SiHa Cells That Differ in Their Response to Transforming Growth Factor-{beta}.
T. T. Maliekal, R. J. Anto, and D. Karunagaran (2004)
J. Biol. Chem. 279, 36287-36292
   Abstract »    Full Text »    PDF »
Role of the Dependence Receptor DCC in Colorectal Cancer Pathogenesis.
P. Mehlen and E. R. Fearon (2004)
J. Clin. Oncol. 22, 3420-3428
   Abstract »    Full Text »    PDF »
Allelic Imbalance of 8p Indicates Poor Survival in Gastric Cancer.
A. J. French, G. Petroni, S. N. Thibideau, M. Smolkin, E. Bissonette, F. Roviello, J. C. Harper, B. R. Koch, S. A. Anderson, S. J. Hebbring, et al. (2004)
J. Mol. Diagn. 6, 243-252
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Targeting Endogenous Transforming Growth Factor {beta} Receptor Signaling in SMAD4-Deficient Human Pancreatic Carcinoma Cells Inhibits Their Invasive Phenotype1.
G. Subramanian, R. E. Schwarz, L. Higgins, G. McEnroe, S. Chakravarty, S. Dugar, and M. Reiss (2004)
Cancer Res. 64, 5200-5211
   Abstract »    Full Text »    PDF »
Amplifying cancer vaccine responses by modifying pathogenic gene programs in tumor cells.
D. E. Spaner (2004)
J. Leukoc. Biol. 76, 338-351
   Abstract »    Full Text »    PDF »
Array Comparative Genomic Hybridization Analysis of Colorectal Cancer Cell Lines and Primary Carcinomas.
E. J. Douglas, H. Fiegler, A. Rowan, S. Halford, D. C. Bicknell, W. Bodmer, I. P. M. Tomlinson, and N. P. Carter (2004)
Cancer Res. 64, 4817-4825
   Abstract »    Full Text »    PDF »
The prevalence of MADH4 and BMPR1A mutations in juvenile polyposis and absence of BMPR2, BMPR1B, and ACVR1 mutations.
J R Howe, M G Sayed, A F Ahmed, J Ringold, J Larsen-Haidle, A Merg, F A Mitros, C A Vaccaro, G M Petersen, F M Giardiello, et al. (2004)
J. Med. Genet. 41, 484-491
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Frequent Silencing of Low Density Lipoprotein Receptor-Related Protein 1B (LRP1B) Expression by Genetic and Epigenetic Mechanisms in Esophageal Squamous Cell Carcinoma.
I. Sonoda, I. Imoto, J. Inoue, T. Shibata, Y. Shimada, K. Chin, M. Imamura, T. Amagasa, J. W. Gray, S. Hirohashi, et al. (2004)
Cancer Res. 64, 3741-3747
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Biologically Different Subgroups of Invasive Ductal Carcinoma of the Pancreas: Dpc4 Status According to the Ratio of Intraductal Carcinoma Components.
H. Takahashi, T. Oda, T. Hasebe, Y. Aoyagi, T. Kinoshita, M. Konishi, T. Nakagohri, K. Inoue, S. Takahashi, H. Kawahira, et al. (2004)
Clin. Cancer Res. 10, 3772-3779
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Down-Regulation of BRCA1 in Chronic Pancreatitis and Sporadic Pancreatic Adenocarcinoma.
C. Beger, M. Ramadani, S. Meyer, G. Leder, M. Kruger, K. Welte, F. Gansauge, and H. G. Beger (2004)
Clin. Cancer Res. 10, 3780-3787
   Abstract »    Full Text »    PDF »
Thioredoxin Is Downstream of Smad7 in a Pathway That Promotes Growth and Suppresses Cisplatin-Induced Apoptosis in Pancreatic Cancer.
N. B. Arnold, K. Ketterer, J. Kleeff, H. Friess, M. W. Buchler, and M. Korc (2004)
Cancer Res. 64, 3599-3606
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Prognostic significance of the expression of Smad4 and Smad7 in human gastric carcinomas.
Y. H. Kim, H. S. Lee, H.-J. Lee, K. Hur, W. H. Kim, Y.-J. Bang, S.-J. Kim, K. U. Lee, K. J. Choe, and H.-K. Yang (2004)
Ann. Onc. 15, 574-580
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Jab1/CSN5, a Component of the COP9 Signalosome, Regulates Transforming Growth Factor {beta} Signaling by Binding to Smad7 and Promoting Its Degradation.
B.-C. Kim, H.-J. Lee, S. H. Park, S. R. Lee, T. S. Karpova, J. G. McNally, A. Felici, D. K. Lee, and S.-J. Kim (2004)
Mol. Cell. Biol. 24, 2251-2262
   Abstract »    Full Text »    PDF »
RUNX3 expression in primary and metastatic pancreatic cancer.
J Li, J Kleeff, A Guweidhi, I Esposito, P O Berberat, T Giese, M W Buchler, and H Friess (2004)
J. Clin. Pathol. 57, 294-299
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Missense Mutations of MADH4: Characterization of the Mutational Hot Spot and Functional Consequences in Human Tumors.
C. A. Iacobuzio-Donahue, J. Song, G. Parmiagiani, C. J. Yeo, R. H. Hruban, and S. E. Kern (2004)
Clin. Cancer Res. 10, 1597-1604
   Abstract »    Full Text »    PDF »


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