Molecular and clinical characteristics in 46 families affected with Peutz-Jeghers syndrome

Digestive Diseases and Sciences

Volumn 52, Issue 8, 2007, Pages 1924-1933

  Mehenni, Hamid ^a,n   Resta, Nicoletta ^b   Guanti, Ginevra ^b   Mota Vieira, Louisa ^c   Lerner, Aaron ^d   Peyman, Mohammed ^e   Chong, Kim A ^f   Aissa, Larbi ^g   Ince, Ali ^h   Cosme, Angel ⁱ   Costanza, Michael C ^j   Rossier, Colette ^k   Radhakrishna, Uppala ^l   Burt, Randall W ^m   Picard, Didier ^a  

^a UNIVERSITY OF GENEVA   (Switzerland)

^b UNIVERSITY OF BARI   (Italy)

^c Hospital de Ponta Delgada   (Portugal)

^d Haifa Hospital   (Israel)

^e ISLAMIC AZAD UNIVERSITY   (Iran)

^f UNIVERSITY OF SÃO PAULO   (Brazil)

^g IBN ROCHD UNIVERSITY HOSPITAL   (Morocco)

^h Haydarpasa Numune Training Hospital   (Turkey)

ⁱ HOSPITAL DONOSTIA   (Spain)

^j GENEVA UNIVERSITY HOSPITALS   (Switzerland)

^k UNIVERSITY OF GENEVA MEDICAL SCHOOL   (Switzerland)

^l Green Cross Voluntary Blood Bank   (India)

^m UNIVERSITY OF UTAH SCHOOL OF MEDICINE   (United States)

ⁿ Centre Medical du Rond point de Plainpalais   (Switzerland)

more..

Author keywords

Cancer; Genotype phenotype analysis; Pathogenic LKB1 STK11 gene mutations; Peutz Jeghers syndrome

Indexed keywords

PROTEIN KINASE LKB1;

ADOLESCENT; ADULT; ANALYTIC METHOD; ARTICLE; BILE DUCT CARCINOMA; CHILD; CLINICAL ARTICLE; CONFORMATION; CONTROLLED STUDY; DNA POLYMORPHISM; FEMALE; GENE DELETION; GENE MUTATION; GENE REARRANGEMENT; GENE SEQUENCE; GENETIC VARIABILITY; GENOTYPE; HETEROZYGOTE; HUMAN; LKB1 GENE; MALE; MISSENSE MUTATION; MOLECULAR BIOLOGY; NONSENSE MUTATION; PEUTZ JEGHERS SYNDROME; PHENOTYPE; PRIORITY JOURNAL; SOUTHERN BLOTTING; STATISTICAL ANALYSIS;

ADENOCARCINOMA; ADOLESCENT; ADULT; AGED; BILE DUCT NEOPLASMS; CHILD; CHROMOSOME DELETION; FEMALE; GENE REARRANGEMENT; GENOTYPE; HUMANS; MALE; MIDDLE AGED; MUTATION; PEUTZ-JEGHERS SYNDROME; PHENOTYPE; POLYMORPHISM, SINGLE-STRANDED CONFORMATIONAL; PROTEIN-SERINE-THREONINE KINASES;

EID: 34347386038     PISSN: 01632116     EISSN: None     Source Type: Journal    
DOI: 10.1007/s10620-006-9435-3     Document Type: Article

References (49)

1. Lindor NM (2004) Recognition of genetic syndromes in families with suspected hereditary colon cancer syndromes. Clin Gastroenterol Hepatol 2:366-375
2. Giardiello FM, Welsh SB, Hamilton SR, Offerhaus GJ, Gittelsohn AM, Booker SV, Krush AJ, Yardley JH, Luk GD (1987) Increased risk of cancer in the Peutz-Jeghers syndrome. N Engl J Med 316:1511-1514
3. Spigelman AD, Murday V, Phillips RK (1989) Cancer and the Peutz-Jeghers syndrome. Gut 30:1588-1590
4. Boardman LA, Thibodeau SN, Schaid DJ, Lindor NM, McDonnell SK, Burgart LJ, Ahlquist DA, Podratz KC, Pittelkow M, Hartmann LC (1998) Increased risk for cancer in patients with the Peutz-Jeghers syndrome. Ann Intern Med 128:896-899
5. Hemminki A, Tomlinson I, Markie D, Jarvinen H, Sistonen P, Bjorkqvist AM, Knuutila S, Salovaara R, Bodmer W, Shibata D, de la Chapelle A, Aaltonen LA (1997) Localization of a susceptibility locus for Peutz-Jeghers syndrome to 19p using comparative genomic hybridization and targeted linkage analysis. Nat Genet 15:87-90
6. Hemminki A, Markie D, Tomlinson I, Avizienyte E, Roth S, Loukola A, Bignell G, Warren W, Aminoff M, Hoglund P, Jarvinen H, Kristo P, Pelin K, Ridanpaa M, Salovaara R, Toro T, Bodmer W, Olschwang S, Olsen AS, Stratton MR, de la Chapelle A, Aaltonen LA (1998) A serine/threonine kinase gene defective in Peutz-Jeghers syndrome. Nature 391:184-187
7. Jenne DE, Reimann H, Nezu J, Friedel W, Loff S, Jeschke R, Muller O, Back W, Zimmer M (1998) Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase. Nat Genet 18:38-43
8. Tiainen M, Ylikorkala A, Makela TP (1999) Growth suppression by Lkb1 is mediated by a G(1) cell cycle arrest. Proc Natl Acad Sci USA 96:9248-9251
9. Mehenni H, Gehrig C, Nezu J, Oku A, Shimane M, Rossier C, Guex N, Blouin JL, Scott HS, Antonarakis SE (1998) Loss of LKB1 kinase activity in Peutz-Jeghers syndrome, and evidence for allelic and locus heterogeneity. Am J Hum Genet 63:1641-1650
10. Ylikorkala A, Avizienyte E, Tomlinson IP, Tiainen M, Roth S, Loukola A, Hemminki A, Johansson M, Sistonen P, Markie D, Neale K, Phillips R, Zauber P, Twama T, Sampson J, Jarvinen H, Makela TP, Aaltonen LA (1999) Mutations and impaired function of LKB1 in familial and non-familial Peutz-Jeghers syndrome and a sporadic testicular cancer. Hum Mol Genet 8:45-51
11. Olschwang S, Markie D, Seal S, Neale K, Phillips R, Cottrell S, Ellis I, Hodgson S, Zauber P, Spigelman A, Iwama T, Loff S, McKeown C, Marchese C, Sampson J, Davies S, Talbot I, Wyke J, Thomas G, Bodmer W, Hemminki A, Avizienyte E, de la Chapelle A, Aaltonen L, Tomlinson I, et al. (1998) Peutz-Jeghers disease: most, but not all, families are compatible with linkage to 19p13.3. J Med Genet 35:42-44
12. Scott RJ, Crooks R, Meldrum CJ, Thomas L, Smith CJ, Mowat D, McPhillips M, Spigelman AD (2002) Mutation analysis of the STK11/LKB1 gene and clinical characteristics of an Australian series of Peutz-Jeghers syndrome patients. Clin Genet 62:282-287
13. Mehenni H, Blouin JL, Radhakrishna U, Bhardwaj SS, Bhardwaj K, Dixit VB, Richards KF, Bermejo-Fenoll A, Leal AS, Raval RC, Antonarakis SE (1997) Peutz-Jeghers syndrome: confirmation of linkage to chromosome 19p13.3 and identification of a potential second locus, on 19q13.4. Am J Hum Genet 61:1327-1334
14. Hearle N, Lucassen A, Wang R, Lim W, Ross F, Wheeler R, Moore I, Shipley J, Houlston R (2004) Mapping of a translocation breakpoint in a Peutz-Jeghers hamartoma to the putative PJS locus at 19q13.4 and mutation analysis of candidate genes in polyp and STK11-negative PJS cases. Genes Chromosomes Cancer 41:163-169
15. Boardman LA, Couch FJ, Burgart LJ, Schwartz D, Berry R, McDonnell SK, Schaid DJ, Hartmann LC, Schroeder JJ, Stratakis CA, Thibodeau SN (2000) Genetic heterogeneity in Peutz-Jeghers syndrome. Hum Mutat 16:23-30
16. Antonarakis SE (1998) Recommendations for a nomenclature system for human gene mutations. Nomenclature Working Group. Hum Mutat 11:1-3
17. Resta N, Simone C, Mareni C, Montera M, Gentile M, Susca F, Gristina R, Pozzi S, Bertario L, Bufo P, Carlomagno N, Ingrosso M, Rossini FP, Tenconi R, Guanti G (1998) STK11 mutations in Peutz-Jeghers syndrome and sporadic colon cancer. Cancer Res 58:4799-4801
18. Wang ZJ, Churchman M, Avizienyte E, McKeown C, Davies S, Evans DG, Ferguson A, Ellis I, Xu WH, Yan ZY, Aaltonen LA, Tomlinson IP (1999) Germline mutations of the LKB1 (STK11) gene in Peutz-Jeghers patients. J Med Genet 36:365-368
19. Westerman AM, Entius MM, Boor PP, Koole R, de Baar E, Offerhaus GJ, Lubinski J, Lindhout D, Halley DJ, de Rooij FW, Wilson JH (1999) Novel mutations in the LKB1/STK11 gene in Dutch Peutz-Jeghers families. Hum Mutat 13:476-481
20. Olschwang S, Boisson C, Thomas G (2001) Peutz-Jeghers families unlinked to STK11/LKB1 gene mutations are highly predisposed to primitive biliary adenocarcinoma. J Med Genet 38:356-360
21. Boudeau J, Kieloch A, Alessi DR, Stella A, Guanti G, Resta N (2003) Functional analysis of LKB1/STK11 mutants and two aberrant isoforms found in Peutz-Jeghers syndrome patients. Hum Mutat 21:172
22. Le Meur N, Martin C, Saugier-Veber P, Joly G, Lemoine F, Moirot H, Rossi A, Bachy B, Cabot A, Joly P, Frebourg T (2004) Complete germline deletion of the STK11 gene in a family with Peutz-Jeghers syndrome. Eur J Hum Genet 12:415-418
23. Lim W, Hearle N, Shah B, Murday V, Hodgson SV, Lucassen A, Eccles D, Talbot I, Neale K, Lim AG, O'Donohue J, Donaldson A, Macdonald RC, Young ID, Robinson MH, Lee PW, Stoodley BJ, Tomlinson I, Alderson D, Holbrook AG, Vyas S, Swarbrick ET, Lewis AA, Phillips RK, Houlston RS (2003) Further observations on LKB1/STK11 status and cancer risk in Peutz-Jeghers syndrome. Br J Cancer 89:308-313
24. Amos CI, Keitheri-Cheteri MB, Sabripour M, Wei C, McGarrity TJ, Seldin MF, Nations L, Lynch PM, Fidder HH, Friedman E, Frazier ML (2004) Genotype-phenotype correlations in Peutz-Jeghers syndrome. J Med Genet 41:327-333
25. Marignani PA, Kanai F, Carpenter CL (2001) LKB1 associates with Brg1 and is necessary for Brg1-induced growth arrest. J Biol Chem 276:32415-32418
26. Saitoh T, Mine T, Katoh M (2002) Molecular cloning and characterization of human GIPC3, a novel gene homologous to human GIPC1 and GIPC2. Int J Oncol 20:577-582
27. Ossipova O, Bardeesy N, DePinho RA, Green JB (2003) LKB1 (XEEK1) regulates Wnt signalling in vertebrate development. Nat Cell Biol 5:889-894
28. Spicer J, Rayter S, Young N, Elliott R, Ashworth A, Smith D (2003) Regulation of the Wnt signalling component PAR1A by the Peutz-Jeghers syndrome kinase LKB1. Oncogene 22:4752-4756
29. Karuman P, Gozani O, Odze RD, Zhou XC, Zhu H, Shaw R, Brien TP, Bozzuto CD, Ooi D, Cantley LC, Yuan J (2001) The Peutz-Jegher gene product LKB1 is a mediator of p53-dependent cell death. Mol Cell 7:1307-1319
30. Smith DP, Rayter SI, Niederlander C, Spicer J, Jones CM, Ashworth A (2001) LIP1, a cytoplasmic protein functionally linked to the Peutz-Jeghers syndrome kinase LKB1. Hum Mol Genet 10:2869-2877
31. Shaw RJ, Bardeesy N, Manning BD, Lopez L, Kosmatka M, DePinho RA, Cantley LC (2004) The LKB1 tumor suppressor negatively regulates mTOR signaling. Cancer Cell 6:91-99
32. Mehenni H, Lin-Marq N, Buchet-Poyau K, Reymond A, Collart MA, Picard D, Antonarakis SE (2005) LKB1 interacts with and phosphorylates PTEN: a functional link between two proteins involved in cancer predisposing syndromes. Hum Mol Genet 14:2209-2219
33. Buchet-Poyau K, Mehenni H, Radhakrishna U, Antonarakis SE (2002) Search for the second Peutz-Jeghers syndrome locus: exclusion of the STK13, PRKCG, KLK10, and PSCD2 genes on chromosome 19 and the STK11IP gene on chromosome 2. Cytogenet Genome Res 97:171-178
34. Alhopuro P, Katajisto P, Lehtonen R, Ylisaukko-Oja SK, Naatsaari L, Karhu A, Westerman AM, Wilson JH, de Rooij FW, Vogel T, Moeslein G, Tomlinson IP, Aaltonen LA, Makela TP, Launonen V (2005) Mutation analysis of three genes encoding novel LKB1-interacting proteins, BRG1, STRADalpha, and MO25alpha, in Peutz-Jeghers syndrome. Br J Cancer 92:1126-1129
35. de Leng WW, Keller JJ, Luiten S, Musler AR, Jansen M, Baas AF, de Rooij FW, Gille JJ, Menko FH, Offerhaus GJ, Weterman MA (2005) STRAD in Peutz-Jeghers syndrome and sporadic cancers. J Clin Pathol 58:1091-1095
36. Bardeesy N, Sinha M, Hezel AF, Signoretti S, Hathaway NA, Sharpless NE, Loda M, Carrasco DR, DePinho RA (2002) Loss of the Lkb1 tumour suppressor provokes intestinal polyposis but resistance to transformation. Nature 419:162-167
37. Jimenez AI, Fernandez P, Dominguez O, Dopazo A, Sanchez-Cespedes M (2003) Growth and molecular profile of lung cancer cells expressing ectopic LKB1: down-regulation of the phosphatidylinositol 3′-phosphate kinase/PTEN pathway. Cancer Res 63:1382-1388
38. Lim W, Olschwang S, Keller JJ, Westerman AM, Menko FH, Boardman LA, Scott RJ, Trimbath J, Giardiello FM, Gruber SB, Gille JJ, Offerhaus GJ, de Rooij FW, Wilson JH, Spigelman AD, Phillips RK, Houlston RS (2004) Relative frequency and morphology of cancers in STK11 mutation carriers. Gastroenterology 126:1788-1794
39. Su GH, Hruban RH, Bansal RK, Bova GS, Tang DJ, Shekher MC, Westerman AM, Entius MM, Goggins M, Yeo CJ, Kern SE (1999) Germline and somatic mutations of the STK11/LKB1 Peutz-Jeghers gene in pancreatic and biliary cancers. Am J Pathol 154:1835-1840
40. Sahin F, Maitra A, Argani P, Sato N, Maehara N, Montgomery E, Goggins M, Hruban RH, Su GH (2003) Loss of Stk11/Lkb1 expression in pancreatic and biliary neoplasms. Mod Pathol 16:686-691
41. Nakanuma Y, Harada K, Kaji K, Terasaki S, Tsuneyama K, Moteki S, Van de Water J, Leung PS, Gershwin ME (1997) Clinicopathological study of primary biliary cirrhosis negative for antimitochondrial antibodies. Liver 17:281-287
42. Holzinger F, Z'Graggen K, Buchler MW (1999) Mechanisms of biliary carcinogenesis: a pathogenetic multi-stage cascade towards cholangiocarcinoma. Ann Oncol 10(suppl 4):122-126
43. Knudson AG Jr (1985) Hereditary cancer, oncogenes, and antioncogenes. Cancer Res 45:1437-1443
44. Trojan J, Brieger A, Raedle J, Esteller M, Zeuzem S (2000) 5'-CpG island methylation of the LKB1/STK11 promoter and allelic loss at chromosome 19p13.3 in sporadic colorectal cancer. Gut 47:272-276
45. Gruber SB, Entius MM, Petersen GM, Laken SJ, Longo PA, Boyer R, Levin AM, Mujumdar UJ, Trent JM, Kinzler KW, Vogelstein B, Hamilton SR, Polymeropoulos MH, Offerhaus GJ, Giardiello FM (1998) Pathogenesis of adenocarcinoma in Peutz-Jeghers syndrome. Cancer Res 58:5267-5270
46. Wang ZJ, Ellis I, Zauber P, Iwama T, Marchese C, Talbot I, Xue WH, Yan ZY, Tomlinson I (1999) Allelic imbalance at the LKB1 (STK11) locus in tumours from patients with Peutz-Jeghers' syndrome provides evidence for a hamartoma-(adenoma)-carcinoma sequence. J Pathol 188:9-13
47. Entius MM, Keller JJ, Westerman AM, van Rees BP, van Velthuysen ML, de Goeij AF, Wilson JH, Giardiello FM, Offerhaus GJ (2001) Molecular genetic alterations in hamartomatous polyps and carcinomas of patients with Peutz-Jeghers syndrome. J Clin Pathol 54:126-131
48. Sato N, Rosty C, Jansen M, Fukushima N, Ueki T, Yeo CJ, Cameron JL, Iacobuzio-Donahue CA, Hruban RH, Goggins M (2001) STK11/LKB1 Peutz-Jeghers gene inactivation in intraductal papillary-mucinous neoplasms of the pancreas. Am J Pathol 159:2017-2022
49. Wang ZJ, Taylor F, Churchman M, Norbury G, Tomlinson I (1998) Genetic pathways of colorectal carcinogenesis rarely involve the PTEN and LKB1 genes outside the inherited hamartoma syndromes. Am J Pathol 153:363-366