| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Regular Articles |
From the Departments of Pathology,*
Urology,
and
Surgery
and the Oncology
Center,§
The Johns Hopkins University School of
Medicine, Baltimore, Maryland; the Department of
Pathology,¶
The Academic Medical
Center, Amsterdam, The Netherlands; and the Department of Internal
Medicine,||
The Academic Hospital, Erasmus University,
Rotterdam, The Netherlands
Peutz-Jeghers syndrome (PJS) is an autosomal-dominant disorder characterized by hamartomatous polyps in the gastrointestinal tract and by pigmented macules of the lips, buccal mucosa, and digits. Less appreciated is the fact that PJS also predisposes patients to an increased risk of gastrointestinal cancer, and pancreatic cancer has been reported in many PJS patients. It was recently shown that germline mutations of the STK11/LKB1 gene are responsible for PJS. We investigated the role of STK11/LKB1 in the development of pancreatic and biliary cancer in patients with and without the PJS. In a PJS patient having a germline splice site mutation in the STK11/LKB1 gene, sequencing analysis of an intestinal polyp and pancreatic cancer from this patient revealed loss of the wild-type allele of the STK11/LKB1 gene in the cancer. Inactivation of STK11/LKB1, by homozygous deletions or somatic sequence mutations coupled with loss of heterozygosity, was also demonstrated in 4–6% of 127 sporadic pancreatic and biliary adenocarcinomas. Our results demonstrate that germline and somatic genetic alterations of the STK11/LKB1 gene may play a causal role in carcinogenesis and that the same gene contributes to the development of both sporadic and familial forms of cancer.
This article has been cited by other articles:
 |
|
 |
|
  H. B. Pearson, A. McCarthy, C. M.P. Collins, A. Ashworth, and A. R. Clarke Lkb1 Deficiency Causes Prostate Neoplasia in the Mouse Cancer Res., April 1, 2008; 68(7): 2223 - 2232. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. F. Hezel, S. Gurumurthy, Z. Granot, A. Swisa, G. C. Chu, G. Bailey, Y. Dor, N. Bardeesy, and R. A. DePinho Pancreatic Lkb1 Deletion Leads to Acinar Polarity Defects and Cystic Neoplasms Mol. Cell. Biol., April 1, 2008; 28(7): 2414 - 2425. [Abstract] [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]
|
|
|
|
 |
|
 R. E Brand, M. M Lerch, W. S Rubinstein, J. P Neoptolemos, D. C Whitcomb, R. H Hruban, T. A Brentnall, H. T Lynch, M. I Canto, and Participants of the Fourth International Symposium Advances in counselling and surveillance of patients at risk for pancreatic cancer Gut, October 1, 2007; 56(10): 1460 - 1469. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Ghaneh, E. Costello, and J. P Neoptolemos Biology and management of pancreatic cancer Gut, August 1, 2007; 56(8): 1134 - 1152. [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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
F. Schonleben, W. Qiu, N. T. Ciau, D. J. Ho, X. Li, J. D. Allendorf, H. E. Remotti, and G. H. Su PIK3CA Mutations in Intraductal Papillary Mucinous Neoplasm/Carcinoma of the Pancreas. Clin. Cancer Res., June 15, 2006; 12(12): 3851 - 3855. [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]
|
|
|
|
 |
|
 S. Kosuga, E. Tashiro, T. Kajioka, M. Ueki, Y. Shimizu, and M. Imoto GSK-3beta Directly Phosphorylates and Activates MARK2/PAR-1 J. Biol. Chem., December 30, 2005; 280(52): 42715 - 42722. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Wei, C. I. Amos, L. C. Stephens, I. Campos, J. M. Deng, R. R. Behringer, A. Rashid, and M. L. Frazier Mutation of Lkb1 and p53 Genes Exert a Cooperative Effect on Tumorigenesis Cancer Res., December 15, 2005; 65(24): 11297 - 11303. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Payne and C. J. Kemp Tumor suppressor genetics Carcinogenesis, December 1, 2005; 26(12): 2031 - 2045. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W W J de Leng, J J Keller, S Luiten, A R Musler, M Jansen, A F Baas, F W M de Rooij, J J P Gille, F H Menko, G J A Offerhaus, et al. STRAD in Peutz-Jeghers syndrome and sporadic cancers J. Clin. Pathol., October 1, 2005; 58(10): 1091 - 1095. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V Schumacher, T Vogel, B Leube, C Driemel, T Goecke, G Moslein, and B Royer-Pokora STK11 genotyping and cancer risk in Peutz-Jeghers syndrome J. Med. Genet., May 1, 2005; 42(5): 428 - 435. [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]
|
|
|
|
|
|
C. A. Iacobuzio-Donahue, M. S. van der Heijden, M. R. Baumgartner, W. J. Troup, J. M. Romm, K. Doheny, E. Pugh, C. J. Yeo, M. G. Goggins, R. H. Hruban, et al. Large-Scale Allelotype of Pancreaticobiliary Carcinoma Provides Quantitative Estimates of Genome-Wide Allelic Loss Cancer Res., February 1, 2004; 64(3): 871 - 875. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. I. Jimenez, P. Fernandez, O. Dominguez, A. Dopazo, and M. Sanchez-Cespedes Growth and Molecular Profile of Lung Cancer Cells Expressing Ectopic LKB1: Down-Regulation of the Phosphatidylinositol 3'-Phosphate Kinase/PTEN Pathway Cancer Res., March 15, 2003; 63(6): 1382 - 1388. [Abstract] [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]
|
|
|
|
|
|
H. Han, D. J. Bearss, L. W. Browne, R. Calaluce, R. B. Nagle, and D. D. Von Hoff Identification of Differentially Expressed Genes in Pancreatic Cancer Cells Using cDNA Microarray Cancer Res., May 1, 2002; 62(10): 2890 - 2896. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Fukushima, N. Sato, T. Ueki, C. Rosty, K. M. Walter, R. E. Wilentz, C. J. Yeo, R. H. Hruban, and M. Goggins Aberrant Methylation of Preproenkephalin and p16 Genes in Pancreatic Intraepithelial Neoplasia and Pancreatic Ductal Adenocarcinoma Am. J. Pathol., May 1, 2002; 160(5): 1573 - 1581. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Sato, C. Rosty, M. Jansen, N. Fukushima, T. Ueki, C. J. Yeo, J. L. Cameron, C. A. Iacobuzio-Donahue, R. H. Hruban, and M. Goggins STK11/LKB1 Peutz-Jeghers Gene Inactivation in Intraductal Papillary-Mucinous Neoplasms of the Pancreas Am. J. Pathol., December 1, 2001; 159(6): 2017 - 2022. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. M. Anderson and J. E. Harris Selected Features of Nonendocrine Pancreatic Cancer Experimental Biology and Medicine, June 1, 2001; 226(6): 521 - 537. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kern, R. Hruban, M. A. Hollingsworth, R. Brand, T. E. Adrian, E. Jaffee, and M. A. Tempero A White Paper: The Product of a Pancreas Cancer Think Tank Cancer Res., June 1, 2001; 61(12): 4923 - 4932. [Full Text] [PDF]
|
|
|
|
|
|
S. Olschwang, C. Boisson, and G. Thomas Peutz-Jeghers families unlinked to STK11/LKB1 gene mutations are highly predisposed to primitive biliary adenocarcinoma J. Med. Genet., June 1, 2001; 38(6): 356 - 360. [Abstract] [Full Text]
|
|
|
|
 |
|
 G. H. Su, R. Bansal, K. M. Murphy, E. Montgomery, C. J. Yeo, R. H. Hruban, and S. E. Kern ACVR1B (ALK4, activin receptor type 1B) gene mutations in pancreatic carcinoma PNAS, March 13, 2001; 98(6): 3254 - 3257. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Tersmette, G. M. Petersen, G. J. A. Offerhaus, F. C. Falatko, K. A. Brune, M. Goggins, E. Rozenblum, R. E. Wilentz, C. J. Yeo, J. L. Cameron, et al. Increased Risk of Incident Pancreatic Cancer Among First-degree Relatives of Patients with Familial Pancreatic Cancer Clin. Cancer Res., March 1, 2001; 7(3): 738 - 744. [Abstract] [Full Text]
|
|
|
|
|
|
E EFTHIMIOU, T CRNOGORAC-JURCEVIC, N R LEMOINE, and T A BRENTNALL Inherited predisposition to pancreatic cancer Gut, February 1, 2001; 48(2): 143 - 147. [Full Text] [PDF]
|
|
|
|
|
|
M M Entius, J J Keller, A M Westerman, B P van Rees, M-L F van Velthuysen, A F P M de Goeij, J H P Wilson, F M Giardiello, and G J A Offerhaus Molecular genetic alterations in hamartomatous polyps and carcinomas of patients with Peutz-Jeghers syndrome J. Clin. Pathol., February 1, 2001; 54(2): 126 - 131. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J Trojan, A Brieger, J Raedle, M Esteller, and S Zeuzem 5'-CpG island methylation of the LKB1/STK11 promoter and allelic loss at chromosome 19p13.3 in sporadic colorectal cancer Gut, August 1, 2000; 47(2): 272 - 276. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. H. Hruban, M. Goggins, J. Parsons, and S. E. Kern Progression Model for Pancreatic Cancer Clin. Cancer Res., August 1, 2000; 6(8): 2969 - 2972. [Full Text]
|
|
|
|
|
|
R. E. Wilentz, M. Goggins, M. Redston, V. A. Marcus, N. V. Adsay, T. A. Sohn, S. S. Kadkol, C. J. Yeo, M. Choti, M. Zahurak, et al. Genetic, Immunohistochemical, and Clinical Features of Medullary Carcinoma of the Pancreas : A Newly Described and Characterized Entity Am. J. Pathol., May 1, 2000; 156(5): 1641 - 1651. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Launonen, E. Avizienyte, A. Loukola, P. Laiho, R. Salovaara, H. Järvinen, J.-P. Mecklin, A. Oku, M. Shimane, H. C. Kim, et al. No Evidence of Peutz-Jeghers Syndrome Gene LKB1 Involvement in Left-sided Colorectal Carcinomas Cancer Res., February 1, 2000; 60(3): 546 - 548. [Abstract] [Full Text]
|
|
|
|
|
|
G. Lal, G. Liu, B. Schmocker, P. Kaurah, H. Ozcelik, S. A. Narod, M. Redston, and S. Gallinger Inherited Predisposition to Pancreatic Adenocarcinoma: Role of Family History and Germ-Line p16, BRCA1, and BRCA2 Mutations Cancer Res., January 1, 2000; 60(2): 409 - 416. [Abstract] [Full Text]
|
|
|
|
|
|
D. C. Connolly, H. Katabuchi, W. A. Cliby, and K. R. Cho Somatic Mutations in the STK11/LKB1 Gene Are Uncommon in Rare Gynecological Tumor Types Associated with Peutz-Jegher’s Syndrome Am. J. Pathol., January 1, 2000; 156(1): 339 - 345. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
