| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Molecular Biology and Genetics |
Departments of Pathology [K. M. M., K. A. B., C. G., R. H. H., S. E. K.] and Oncology [C. G., J. E. S., R. H. H., S. E. K.], The Johns Hopkins Medical Institutions, Baltimore, Maryland 21231, and The Mayo Clinic, Rochester, Minnesota 55905 [G. M. P.]
It is estimated that familial aggregation and genetic susceptibility play a role in as many as 10% of pancreatic ductal adenocarcinomas. To investigate the role of germ-line mutations in the etiology of pancreatic cancer, we have analyzed samples from patients with pancreatic cancer enrolled in the NFPTR for mutations in four tumor suppressor candidate genes: (a) MAP2K4; (b) MADH4; (c) ACVR1B; and (d) BRCA2 by direct sequencing of constitutional DNA. These genes are mutated in clinically sporadic pancreatic cancer, but germ-line mutations are either not reported or anecdotal in familial pancreatic cancer. Pancreatic cancer patient samples were selected from kindreds in which three or more family members were affected with pancreatic cancer, at least two of which were first-degree relatives. No mutations were identified in mitogen-activated protein kinase kinase 4 (0 of 22), MADH4 (0 of 22), or ACVR1B (0 of 29), making it unlikely that germ-line mutations in these genes account for a significant number of inherited pancreatic cancers. BRCA2 gene sequencing identified five mutations (5 of 29, 17.2%) that are believed to be deleterious and one point mutation (M192T) unreported previously. Three patients harbored the common 6174delT frameshift mutation, one had the splice site mutation IVS 16–2A > G, and one had the splice site mutation IVS 15–1G > A. Two of the five BRCA2 mutation carriers reported a family history of breast cancer, and none reported a family history of ovarian cancer. These findings confirm the increased risk of pancreatic cancer in individuals with BRCA2 mutations and identify germ-line BRCA2 mutations as the most common inherited genetic alteration yet identified in familial pancreatic cancer.
This article has been cited by other articles:
|
|
 |
|
  G. Feldmann and A. Maitra Molecular Genetics of Pancreatic Ductal Adenocarcinomas and Recent Implications for Translational Efforts J. Mol. Diagn., March 1, 2008; 10(2): 111 - 122. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Wang, C. Szabo, C. Qian, P. G. Amadio, S. N. Thibodeau, J. R. Cerhan, G. M. Petersen, W. Liu, and F. J. Couch Mutational Analysis of Thirty-two Double-Strand DNA Break Repair Genes in Breast and Pancreatic Cancers Cancer Res., February 15, 2008; 68(4): 971 - 975. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Wang, S. Chen, K. A. Brune, R. H. Hruban, G. Parmigiani, and A. P. Klein In Reply J. Clin. Oncol., November 20, 2007; 25(33): 5337 - 5338. [Full Text] [PDF]
|
|
|
|
 |
|
 T. Abe, N. Fukushima, K. Brune, C. Boehm, N. Sato, H. Matsubayashi, M. Canto, G. M. Petersen, R. H. Hruban, and M. Goggins Genome-Wide Allelotypes of Familial Pancreatic Adenocarcinomas and Familial and Sporadic Intraductal Papillary Mucinous Neoplasms Clin. Cancer Res., October 15, 2007; 13(20): 6019 - 6025. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. B Greer and D. C Whitcomb Role of BRCA1 and BRCA2 mutations in pancreatic cancer Gut, May 1, 2007; 56(5): 601 - 605. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Wang, S. Chen, K. A. Brune, R. H. Hruban, G. Parmigiani, and A. P. Klein PancPRO: Risk Assessment for Individuals With a Family History of Pancreatic Cancer J. Clin. Oncol., April 10, 2007; 25(11): 1417 - 1422. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Gallmeier, T. Hucl, J. R. Brody, D. A. Dezentje, K. Tahir, J. Kasparkova, V. Brabec, K. E. Bachman, and S. E. Kern High-Throughput Screening Identifies Novel Agents Eliciting Hypersensitivity in Fanconi Pathway-Deficient Cancer Cells Cancer Res., March 1, 2007; 67(5): 2169 - 2177. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. J. Couch, M. R. Johnson, K. G. Rabe, K. Brune, M. de Andrade, M. Goggins, H. Rothenmund, S. Gallinger, A. Klein, G. M. Petersen, et al. The Prevalence of BRCA2 Mutations in Familial Pancreatic Cancer Cancer Epidemiol. Biomarkers Prev., February 1, 2007; 16(2): 342 - 346. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Gallmeier and S. E. Kern Targeting Fanconi Anemia/BRCA2 Pathway Defects in Cancer: The Significance of Preclinical Pharmacogenomic Models Clin. Cancer Res., January 1, 2007; 13(1): 4 - 10. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Earl, L. Yan, L. J. Vitone, J. Risk, S. J. Kemp, C. McFaul, J. P. Neoptolemos, W. Greenhalf, for the European Registry of Hereditary Pancreatit, R. Kress, et al. Evaluation of the 4q32-34 locus in European familial pancreatic cancer. Cancer Epidemiol. Biomarkers Prev., October 1, 2006; 15(10): 1948 - 1955. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. F. Hezel, A. C. Kimmelman, B. Z. Stanger, N. Bardeesy, and R. A. DePinho Genetics and biology of pancreatic ductal adenocarcinoma. Genes & Dev., May 15, 2006; 20(10): 1218 - 1249. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. M. Petersen, M. de Andrade, M. Goggins, R. H. Hruban, M. Bondy, J. F. Korczak, S. Gallinger, H. T. Lynch, S. Syngal, K. G. Rabe, et al. Pancreatic cancer genetic epidemiology consortium. Cancer Epidemiol. Biomarkers Prev., April 1, 2006; 15(4): 704 - 710. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Jimeno and M. Hidalgo Molecular biomarkers: their increasing role in the diagnosis, characterization, and therapy guidance in pancreatic cancer. Mol. Cancer Ther., April 1, 2006; 5(4): 787 - 796. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Matsubayashi, M. Canto, N. Sato, A. Klein, T. Abe, K. Yamashita, C. J. Yeo, A. Kalloo, R. Hruban, and M. Goggins DNA Methylation Alterations in the Pancreatic Juice of Patients with Suspected Pancreatic Disease Cancer Res., January 15, 2006; 66(2): 1208 - 1217. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. H. Hruban, A. K. Rustgi, T. A. Brentnall, M. A. Tempero, C. V. Wright, and D. A. Tuveson Pancreatic Cancer in Mice and Man: The Penn Workshop 2004 Cancer Res., January 1, 2006; 66(1): 14 - 17. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C J van Asperen, R M Brohet, E J Meijers-Heijboer, N Hoogerbrugge, S Verhoef, H F A Vasen, M G E M Ausems, F H Menko, E B Gomez Garcia, J G M Klijn, et al. Cancer risks in BRCA2 families: estimates for sites other than breast and ovary J. Med. Genet., September 1, 2005; 42(9): 711 - 719. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Goggins Molecular Markers of Early Pancreatic Cancer J. Clin. Oncol., July 10, 2005; 23(20): 4524 - 4531. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Pancreatic Section Guidelines for the management of patients with pancreatic cancer periampullary and ampullary carcinomas Gut, June 1, 2005; 54(suppl_5): v1 - v16. [Full Text] [PDF]
|
|
|
|
|
|
F. J. Couch, M. R. Johnson, K. Rabe, L. Boardman, R. McWilliams, M. de Andrade, and G. Petersen Germ Line Fanconi Anemia Complementation Group C Mutations and Pancreatic Cancer Cancer Res., January 15, 2005; 65(2): 383 - 386. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Garber and K. Offit Hereditary Cancer Predisposition Syndromes J. Clin. Oncol., January 10, 2005; 23(2): 276 - 292. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Van der Heijden, J. R. Brody, E. Gallmeier, S. C. Cunningham, D. A. Dezentje, D. Shen, R. H. Hruban, and S. E. Kern Functional Defects in the Fanconi Anemia Pathway in Pancreatic Cancer Cells Am. J. Pathol., August 1, 2004; 165(2): 651 - 657. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Beger, M. Ramadani, S. Meyer, G. Leder, M. Kruger, K. Welte, F. Gansauge, and H. G. Beger Down-Regulation of BRCA1 in Chronic Pancreatitis and Sporadic Pancreatic Adenocarcinoma Clin. Cancer Res., June 1, 2004; 10(11): 3780 - 3787. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. B. Lowenfels and P. Maisonneuve Epidemiology and Prevention of Pancreatic Cancer Jpn. J. Clin. Oncol., May 1, 2004; 34(5): 238 - 244. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Koopmann, P. Buckhaults, D. A. Brown, M. L. Zahurak, N. Sato, N. Fukushima, L. J. Sokoll, D. W. Chan, C. J. Yeo, R. H. Hruban, et al. Serum Macrophage Inhibitory Cytokine 1 as a Marker of Pancreatic and Other Periampullary Cancers Clin. Cancer Res., April 1, 2004; 10(7): 2386 - 2392. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Koopmann, N. S. Fedarko, A. Jain, A. Maitra, C. Iacobuzio-Donahue, A. Rahman, R. H. Hruban, C. J. Yeo, and M. Goggins Evaluation of Osteopontin as Biomarker for Pancreatic Adenocarcinoma Cancer Epidemiol. Biomarkers Prev., March 1, 2004; 13(3): 487 - 491. [Abstract] [Full Text]
|
|
|
|
|
|
A. Liede, B. Y. Karlan, and S. A. Narod Cancer Risks for Male Carriers of Germline Mutations in BRCA1 or BRCA2: A Review of the Literature J. Clin. Oncol., February 15, 2004; 22(4): 735 - 742. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. van der Heijden, R. H. Hruban, and S. E. Kern Reply Cancer Res., October 15, 2003; 63(20): 6999 - 7001. [Full Text] [PDF]
|
|
|
|
|
|
T. A. Dragani 10 Years of Mouse Cancer Modifier Loci: Human Relevance Cancer Res., June 15, 2003; 63(12): 3011 - 3018. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. van der Heijden, C. J. Yeo, R. H. Hruban, and S. E. Kern Fanconi Anemia Gene Mutations in Young-onset Pancreatic Cancer Cancer Res., May 15, 2003; 63(10): 2585 - 2588. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Hempen, L. Zhang, R. K. Bansal, C. A. Iacobuzio-Donahue, K. M. Murphy, A. Maitra, B. Vogelstein, R. H. Whitehead, S. D. Markowitz, J. K. V. Willson, et al. Evidence of Selection for Clones Having Genetic Inactivation of the Activin A Type II Receptor (ACVR2) Gene in Gastrointestinal Cancers Cancer Res., March 1, 2003; 63(5): 994 - 999. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Domchek, A. Eisen, K. Calzone, J. Stopfer, A. Blackwood, and B. L. Weber Application of Breast Cancer Risk Prediction Models in Clinical Practice J. Clin. Oncol., February 15, 2003; 21(4): 593 - 601. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. M. Petersen and R. H. Hruban Familial Pancreatic Cancer: Where Are We in 2003? J Natl Cancer Inst, February 5, 2003; 95(3): 180 - 181. [Full Text] [PDF]
|
|
|
|
|
|
S. A. Hahn, B. Greenhalf, I. Ellis, M. Sina-Frey, H. Rieder, B. Korte, B. Gerdes, R. Kress, A. Ziegler, J. A. Raeburn, et al. BRCA2 Germline Mutations in Familial Pancreatic Carcinoma J Natl Cancer Inst, February 5, 2003; 95(3): 214 - 221. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
