Germline Inactivation of PTEN and Dysregulation of the Phosphoinositol-3- Kinase/Akt Pathway Cause Human Lhermitte-Duclos Disease in Adults

American Journal of Human Genetics

Volumn 73, Issue 5, 2003, Pages 1191-1198

  Zhou, Xiao Ping ^a   Marsh, Deborah J ^c,e   Morrison, Carl D ^a,b   Chaudhury, Abhik R ^b   Maxwell, Marius ^d   Reifenberger, Guido ^f   Eng, Charis ^a,b,g  

^a OHIO STATE UNIVERSITY   (United States)

^b OHIO STATE UNIVERSITY   (United States)

^c DANA FARBER CANCER INSTITUTE   (United States)

^d MASSACHUSETTS GENERAL HOSPITAL   (United States)

^e UNIVERSITY OF SYDNEY   (Australia)

^f HEINRICH HEINE UNIVERSITY   (Germany)

^g UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

PARAFFIN; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN KINASE B;

ADULT; ARTICLE; CLINICAL ARTICLE; ENZYME INACTIVATION; FAMILIAL DISEASE; GANGLIONEUROMA; GENE MUTATION; GENETIC ANALYSIS; HUMAN; IMMUNOHISTOCHEMISTRY; LHERMITTE DUCLOS DISEASE; PRIORITY JOURNAL; PROTEIN DEFECT; PROTEIN EXPRESSION; PROTEIN FUNCTION;

EID: 0242522403     PISSN: 00029297     EISSN: None     Source Type: Journal    
DOI: 10.1086/379382     Document Type: Article

References (47)

1. Albrecht S, Haber RM, Goodman JC, Duvic, M (1992) Cowden syndrome and Lhermitte-Duclos disease. Cancer 70: 869-876
2. Ambler M, Pogacar S, Sidman R (1969) Lhermitte-Duclos disease (granule cell hypertrophy of the cerebellum) pathological analysis of the first familial cases. J Neuropathol Exp Neurol 28:622-647
3. Backman SA, Stambolic V, Suzuki A, Haight J, Elia A, Pretorius J, Tsao MS, Shannon P, Bolon B, Ivy GO, Mak TW (2001) Deletion of Pten in mouse brain causes seizures, ataxia and defects in soma size resembling Lhermitte-Duclos disease. Nat Genet 29:396-403
4. Capone Mori A, Hoeltzenbein M, Poetsch M, Schneider JF, Brandner S, Boltshauser E (2003) Lhermitte-duclos disease in 3 children: a clinical long-term observation. Neuropediatrics 34:30-35
5. Eng C (2000) Will the real Cowden syndrome please stand up: revised diagnostic criteria. J Med Genet 37:828-830
6. Eng C (2003) PTEN: one gene, many syndromes. Hum Mutat (in press)
7. Eng C, Murday V, Seal S, Mohammed S, Hodgson SV, Chaudary MA, Fentiman IS, Ponder BA, Eeles RA (1994) Cowden syndrome and Lhermitte-Duclos disease in a family: a single genetic syndrome with pleiotropy? J Med Genet 31:458-461
8. Furnari FB, Huang HJ, Cavenee WK (1998) The phosphoinositol phosphatase activity of PTEN mediates a serum-sensitive G1 growth arrest in glioma cells. Cancer Res 58:5002-5008
9. Gimm O, Perren A, Weng LP, Marsh DJ, Yeh JJ, Ziebold U, Gil E, Hinze R, Delbridge L, Lees JA, Mutter GL, Robinson BG, Komminoth P, Dralle H, Eng C (2000) Differential nuclear and cytoplasmic expression of PTEN in normal thyroid tissue, and benign and malignant epithelial thyroid tumors. Am J Pathol 156:1693-1700
10. Iida S, Tanaka Y, Fujii H, Hayashi S, Kimura M, Nagareda T, Moriwaki K (1998) A heterozygous frameshift mutation of the PTEN/MMAC1 gene in a patient with Lhermitte-Duclos disease - only the mutated allele was expressed in the cerebellar tumor. Int J Mol Med 1:925-929
11. Koch R, Scholz M, Nelen MR, Schwechheimer K, Epplen JT, Harders AG (1999) Lhermitte-Duclos disease as a component of Cowden's syndrome: case report and review of the literature. J Neurosurg 90:776-779
12. Kurose K, Gilley K, Matsumoto S, Watson PH, Zhou XP, Eng C (2002) Frequent somatic mutations in PTEN and TP53 are mutually exclusive in the stroma of breast carcinomas. Nat Genet 32:355-357
13. Kwon CH, Zhu X, Zhang J, Knoop LL, Tharp R, Smeyne RJ, Eberhart CG, Burger PC, Baker SJ (2001) Pten regulates neuronal soma size: a mouse model of Lhermitte-Duclos disease. Nat Genet 29:404-411
14. Li DM, Sun H (1997) TEP1, encoded by a candidate tumor suppressor locus, is a novel protein tyrosine phosphatase regulated by transforming growth factor beta. Cancer Res 57:2124-2129
15. Li DM, Sun H (1998) PTEN/MMAC1/TEP1 suppresses the tumorigenicity and induces G1 cell cycle arrest in human glioblastoma cells. Proc Natl Acad Sci USA 95:15406-15411
16. Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Miliaresis C, Rodgers L, McCombie R, Bigner SH, Giovanella BC, Ittmann M, Tycko B, Hibshoosh H, Wigler MH, Parsons R (1997) PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 275:1943-1947
17. Liaw D, Marsh DJ, Li J, Dahia PL, Wang SI, Zheng Z, Bose S, Call KM, Tsou HC, Peacocke M, Eng C, Parsons R (1997) Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. Nat Genet 16:64-67
18. Maehama T, Dixon JE (1998) The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem 273:13375-13378
19. Marsh DJ, Coulon V, Lunetta KL, Rocca-Serra P, Dahia PL, Zheng Z, Liaw D, Caron S, Duboue B, Lin AY, Richardson AL, Bonnetblanc JM, Bressieux JM, Cabarrot-Moreau A, Chompret A, Demange L, Eeles RA, Yahanda AM, Fearon ER, Fricker JP, Gorlin RJ, Hodgson SV, Huson S, Lacombe D, Eng C, et al. (1998) Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation. Hum Mol Genet 7:507-515
20. Marsh DJ, Dahia PL, Zheng Z, Liaw D, Parsons R, Gorlin RJ, Eng C (1997) Germline mutations in PTEN are present in Bannayan-Zonana syndrome. Nat Genet 16:333-334
21. Marsh DJ, Kum JB, Lunetta KL, Bennett MJ, Gorlin RJ, Ahmed SF, Bodurtha J, Crowe C, Curtis MA, Dasouki M, Dunn T, Feit H, Geraghty MT, Graham JM Jr, Hodgson SV, Hunter A, Korf BR, Manchester D, Miesfeldt S, Murday VA, Nathanson KL, Parisi M, Pober B, Romano C, Eng C, et al (1999) PTEN mutation spectrum and genotype-phenotype correlations in Bannayan-Riley-Ruvalcaba syndrome suggest a single entity with Cowden syndrome. Hum Mol Genet 8:1461-1472
22. Mutter GL, Lin MC, Fitzgerald JT, Kum JB, Baak JP, Lees JA, Weng LP, Eng C (2000) Altered PTEN expression as a diagnostic marker for the earliest endometrial precancers. J Natl Cancer Inst 92:924-930
23. Nelen MR, Kremer H, Konings IB, Schoute F, van Essen AJ, Koch R, Woods CG, Fryns JP, Hamel B, Hoefsloot LH, Peeters EA, Padberg GW (1999) Novel PTEN mutations in patients with Cowden disease: absence of clear genotype-phenotype correlations. Eur J Hum Genet 7:267-273
24. Nelen MR, van Staveren WC, Peeters EA, Hassel MB, Gorlin RJ, Hamm H, Lindboe CF, Fryns JP, Sijmons RH, Woods DG, Mariman EC, Padberg GW, Kremer H (1997) Germline mutations in the PTEN/MMAC1 gene in patients with Cowden disease. Hum Mol Genet 6:1383-1387
25. Nowak DA, Trost HA (2002) Lhermitte-Duclos disease (dysplastic cerebellar gangliocytoma): a malformation, hamartoma or neoplasm? Acta Neurol Scand 105:137-145
26. Padberg GW, Schot JD, Vielvoye GJ, Bots GT, de Beer FC (1991) Lhermitte-Duclos disease and Cowden disease: a single phakomatosis. Ann Neurol 29:517-523
27. Perren A, Komminoth P, Saremaslani P, Matter C, Feurer S, Lees JA, Heitz PU, Eng C (2000) Mutation and expression analyses reveal differential subcellular compartmentalization of PTEN in endocrine pancreatic tumors compared to normal islet cells. Am J Pathol 157:1097-1103
28. Perren A, Weng LP, Boag AH, Ziebold U, Thakore K, Dahia PL, Komminoth P, Lees JA, Mulligan LM, Mutter GL, Eng C (1999) Immunohistochemical evidence of loss of PTEN expression in primary ductal adenocarcinomas of the breast. Am J Pathol 155:1253-1260
29. Reardon W, Zhou XP, Eng C (2001) A novel germline mutation of the PTEN gene in a patient with macrocephaly, ventricular dilatation, and features of VATER association. J Med Genet 38:820-823
30. Robinson S, Cohen AR (2000) Cowden disease and Lhermitte-Duclos disease: characterization of a new phakomatosis. Neurosurgery 46:371-383
31. Russell-Jones R, O'Brien M, Wells RS (1981) Cowden syndrome. Br J Dermatol 105:57-58
32. Smith JM, Kirk EP, Theodosopoulos G, Marshall GM, Walker J, Rogers M, Field M, Brereton JJ, Marsh DJ (2002) Germline mutation of the tumour suppressor PTEN in Proteus syndrome. J Med Genet 39:937-940
33. Stambolic V, Suzuki A, de la Pompa JL, Brothers GM, Mirtsos C, Sasaki T, Ruland J, Penninger JM, Siderovski DP, Mak TW (1998) Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN. Cell 95:29-39.
34. Steck PA, Pershouse MA, Jasser SA, Yung WK, Lin H, Ligon AH, Langford LA, Baumgard ML, Hattier T, Davis T, Frye C, Hu R, Swedlund B, Teng DH, Tavtigian SV (1997) Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat Genet 15:356-362
35. Sutphen R, Diamond TM, Minton SE, Peacocke M, Tsou HC, Root AW (1999) Severe Lhermitte-Duclos disease with unique germline mutation of PTEN. Am J Med Genet 82:290-293
36. Vinchon M, Blond S, Lejeune JP, Krivosik I, Fossati P, Assaker R, Christiaens JL (1994) Association of Lhermitte-Duclos and Cowden disease: report of a new case and review of the literature. J Neurol Neurosurg Psychiatry 57:699-704
37. Weng L, Brown J, Eng C (2001a) PTEN induces apoptosis and cell cycle arrest through phosphoinositol-3-kinase/Akt-dependent and -independent pathways. Hum Mol Genet 10:237-242
38. Weng LP, Brown JL, Baker KM, Ostrowski MC, Eng C (2002) PTEN blocks insulin-mediated ETS-2 phosphorylation through MAP kinase, independently of the phosphoinositide 3-kinase pathway. Hum Mol Genet 11:1687-1696
39. Weng LP, Brown JL, Eng C (2001b) PTEN coordinates G(1) arrest by down-regulating cyclin D1 via its protein phosphatase activity and up-regulating p27 via its lipid phosphatase activity in a breast cancer model. Hum Mol Genet 10:599-604
40. Weng LP, Gimm O, Kum JB, Smith WM, Zhou XP, Wynford-Thomas D, Leone G, Eng C (2001c) Transient ectopic expression of PTEN in thyroid cancer cell lines induces cell cycle arrest and cell type-dependent cell death. Hum Mol Genet 10:251-258
41. Weng LP, Smith WM, Brown JL, Eng C (2001d) PTEN inhibits insulin-stimulated MEK/MAPK activation and cell growth by blocking IRS-1 phosphorylation and IRS-1/Grb-2/Sos complex formation in a breast cancer model. Hum Mol Genet 10:605-616
42. Weng LP, Smith WM, Dahia PL, Ziebold U, Gil E, Lees JA, Eng C (1999) PTEN suppresses breast cancer cell growth by phosphatase activity-dependent G1 arrest followed by cell death. Cancer Res 59:5808-5814
43. Zhou XP, Hampel H, Thiele H, Gorlin RJ, Hennekam RC, Parisi M, Winter RM, Eng C (2001) Association of germline mutation in the PTEN tumour suppressor gene and Proteus and Proteus-like syndromes. Lancet 358:210-211
44. Zhou XP, Gimm O, Hampel H, Niemann T, Walker MJ, Eng C (200Oa) Epigenetic PTEN silencing in malignant melanomas without PTEN mutation. Am J Pathol 157:1123-1128
45. Zhou XP, Loukola A, Salovaara R, Nystrom-Lahti M, Peltomaki P, de la Chapelle A, Aaltonen LA, Eng C (2002) PTEN mutational spectra, expression levels, and subcellular localization in microsatellite stable and unstable colorectal cancers. Am J Pathol 161:439-447
46. Zhou XP, Marsh DJ, Hampel H, Mulliken JB, Gimm O, Eng C (2000b) Germline and germline mosaic PTEN mutations associated with a Proteus-like syndrome of hemihypertrophy, lower limb asymmetry, arteriovenous malformations and lipomatosis. Hum Mol Genet 9:765-768
47. Zhou XP, Waite KA, Pilarski R, Hampel H, Fernandez MJ, Bos C, Dasouki M, Feldman GL, Greenberg LA, Ivanovich J, Matloff E, Patterson A, Pierpont ME, Russo D, Nassif NT, Eng C (2003) Germline PTEN promoter mutations and deletions in Cowden/Bannayan-Riley-Ruvalcaba syndrome result in aberrant PTEN protein and dysregulation of the phosphoinositol-3-kinase/Akt pathway. Am J Hum Genet 73:404-411