Genetic predisposition to peripheral nerve neoplasia: Diagnostic criteria and pathogenesis of neurofibromatoses, Carney complex, and related syndromes

Acta Neuropathologica

Volumn 123, Issue 3, 2012, Pages 349-367

  Rodriguez, Fausto J ^a   Stratakis, Constantine A ^b   Evans, D Gareth ^c  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT   (United States)

^c ST MARY S HOSPITAL   (United Kingdom)

Author keywords

Carney complex; Multiple endocrine neoplasia; Neurofibroma; Neurofibromatosis; NF1; NF2; Schwannoma; Schwannomatosis

Indexed keywords

NEUROFIBROMIN;

CARCINOGENESIS; CARNEY COMPLEX; CENTRAL NERVOUS SYSTEM DISEASE; CLINICAL FEATURE; DISEASE ASSOCIATION; DISEASE COURSE; ENDOCRINE DISEASE; GENE DELETION; GENE FREQUENCY; GENE FUNCTION; GENE IDENTIFICATION; GENE LOSS; GENE MUTATION; GENE PRODUCT; GENE SEQUENCE; GENETIC ASSOCIATION; GENETIC LINKAGE; GENETIC PREDISPOSITION; HAMARTOMA; HAPLOINSUFFICIENCY; HUMAN; INI1 GENE; MEN2B GENE; MOLECULAR DIAGNOSIS; MOLECULAR PATHOLOGY; MORBIDITY; MULTIPLE ORGAN FAILURE; MUSCULOSKELETAL DISEASE; NEUROFIBROMATOSIS; NF1 GENE; NF2 GENE; NONSENSE MEDIATED MRNA DECAY; PERIPHERAL NERVE TUMOR; PERIPHERAL NEUROPATHY; PRIORITY JOURNAL; PROTEIN EXPRESSION; RET GENE; REVIEW; SCHWANNOMATOSIS; SKIN DISEASE; SMARCB1 GENE; TUMOR CLASSIFICATION; TUMOR DIAGNOSIS; TUMOR SUPPRESSOR GENE;

CARNEY COMPLEX; GENETIC PREDISPOSITION TO DISEASE; HUMANS; NEUROFIBROMATOSES; PERIPHERAL NERVES; PERIPHERAL NERVOUS SYSTEM NEOPLASMS; SKIN;

EID: 84857918921     PISSN: 00016322     EISSN: 14320533     Source Type: Journal    
DOI: 10.1007/s00401-011-0935-7     Document Type: Review

References (125)

1. (1988) National Institutes of Health Consensus Development Conference Statement: Neurofibromatosis. Arch Neurol 45:575-578
2. (1994) Consensus Development Panel, National Institutes of Health Consensus Development Conference Statement n Acoustic Neuroma. Arch Neurol 51:201-207
3. Almeida MQ, Muchow M, Boikos S, Bauer AJ, Griffin KJ, Tsang KM, Cheadle C, Watkins T, Wen F, Starost MF, Bossis I, Nesterova M, Stratakis CA (2010) Mouse Prkar1a haploinsufficiency leads to an increase in tumors in the Trp53 ± or Rb1 ±backgrounds and chemically induced skin papillomas by dysregulation of the cell cycle and Wnt signaling. Hum Mol Genet 19:1387-1398
4. Amieux PS, Cummings DE, Motamed K, Brandon EP, Wailes LA, Le K, Idzerda RL, McKnight GS (1997) Compensatory regulation of RIalpha protein levels in protein kinase A mutant mice. J Biol Chem 272:3993-3998
5. Antinheimo J, Sankila R, Carpen O, Pukkala E, Sainio M, Jaaskelainen J (2000) Population-based analysis of sporadic and type 2 neurofibromatosis- associated meningiomas and schwannomas. Neurology 54:71-76 (Pubitemid 30038740)
6. Atherton DJ, Pitcher DW, Wells RS, MacDonald DM (1980) A syndrome of various cutaneous pigmented lesions, myxoid neurofibromata and atrial myxoma: the NAME syndrome. Br J Dermatol 103:421-429 (Pubitemid 10029498)
7. Bacci C, Sestini R, Provenzano A, Paganini I, Mancini I, Porfirio B, Vivarelli R, Genuardi M, Papi L (2010) Schwannomatosis associated with multiple meningiomas due to a familial SMARCB1 mutation. Neurogenetics 11:73-80
8. Baser ME, Friedman JM, Joe H, Shenton A, Wallace AJ, Ramsden RT, Evans DG (2011) Empirical development of improved diagnostic criteria for neurofibromatosis 2. Genet Med 13:576-581
9. Benhamouche S, Curto M, Saotome I, Gladden AB, Liu CH, Giovannini M, McClatchey AI (2010) Nf2/Merlin controls progenitor homeostasis and tumorigenesis in the liver. Genes Dev 24:1718-1730
10. Bertherat J, Horvath A, Groussin L, Grabar S, Boikos S, Cazabat L, Libe R, Rene-Corail F, Stergiopoulos S, Bourdeau I, Bei T, Clauser E, Calender A, Kirschner LS, Bertagna X, Carney JA, Stratakis CA (2009) Mutations in regulatory subunit type 1A of cyclic adenosine 5′-monophosphate-dependent protein kinase (PRKAR1A): phenotype analysis in 353 patients and 80 different genotypes. J Clin Endocrinol Metab 94:2085-2091
11. Biegel JA, Zhou JY, Rorke LB, Stenstrom C, Wainwright LM, Fogelgren B (1999) Germ-line and acquired mutations of INI1 in atypical teratoid and rhabdoid tumors. Cancer Res 59:74-79 (Pubitemid 29062960)
12. Boikos SA, Stratakis CA (2006) Carney complex: pathology and molecular genetics. Neuroendocrinology 83:189-199 (Pubitemid 44578871)
13. Bossis I, Voutetakis A, Bei T, Sandrini F, Griffin KJ, Stratakis CA (2004) Protein kinase A and its role in human neoplasia: the Carney complex paradigm. Endocr Relat Cancer 11:265-280 (Pubitemid 38832829)
14. Bradbury AW, Carter DC, Miller WR, Cho-Chung YS, Clair T (1994) Protein kinase A (PK-A) regulatory subunit expression in colorectal cancer and related mucosa. Br J Cancer 69:738-742 (Pubitemid 24112697)
15. Brems H, Chmara M, Sahbatou M, Denayer E, Taniguchi K, Kato R, Somers R, Messiaen L, De Schepper S, Fryns JP, Cools J, Marynen P, Thomas G, Yoshimura A, Legius E (2007) Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis 1-like phenotype. Nat Genet 39:1120-1126 (Pubitemid 47340658)
16. Brems H, Park C, Maertens O, Pemov A, Messiaen L, Upadhyaya M, Claes K, Beert E, Peeters K, Mautner V, Sloan JL, Yao L, Lee CC, Sciot R, De Smet L, Legius E, Stewart DR (2009) Glomus tumors in neurofibromatosis type 1: genetic, functional, and clinical evidence of a novel association. Cancer Res 69:7393-7401
17. Buchanan ME, Davis RL (2010) A distinct set of Drosophila brain neurons required for neurofibromatosis type 1-dependent learning and memory. J Neurosci 30:10135-10143
18. Carney JA (1990) Psammomatous melanotic schwannoma. A distinctive, heritable tumor with special associations, including cardiac myxoma and the Cushing syndrome. Am J Surg Pathol 14:206-222
19. Carney JA, Stratakis CA (1998) Epithelioid blue nevus and psammomatous melanotic schwannoma: the unusual pigmented skin tumors of the Carney complex. Semin Diagn Pathol 15:216-224 (Pubitemid 28369196)
20. Carroll S (2012) Molecular mechanisms promoting the pathogenesis of Schwann cell neoplasms. Acta Neuropathol
21. Casey M, Vaughan CJ, He J, Hatcher CJ, Winter JM, Weremowicz S, Montgomery K, Kucherlapati R, Morton CC, Basson CT (2000) Mutations in the protein kinase A R1alpha regulatory subunit cause familial cardiac myxomas and Carney complex. J Clin Invest 106:R31-R38
22. Cawthon RM, Weiss R, Xu GF, Viskochil D, Culver M, Stevens J, Robertson M, Dunn D, Gesteland R, O'Connell P et al (1990) A major segment of the neurofibromatosis type 1 gene: cDNA sequence, genomic structure, and pointmutations. Cell 62:193-201
23. Christiaans I, Kenter SB, Brink HC, van Os TA, Baas F, van den Munckhof P, Kidd AM, Hulsebos TJ (2011) Germline SMARCB1 mutation and somatic NF2 mutations in familial multiple meningiomas. J Med Genet 48:93-97
24. Cichowski K, Jacks T (2001) NF1 tumor suppressor gene function: narrowing the GAP. Cell 104:593-604 (Pubitemid 32201953)
25. Cras P, Ceuterick-de Groote C, Van Vyve M, Vercruyssen A, Martin JJ (1990) Malignant pigmented spinal nerve root schwannoma metastasizing in the brain and viscera. Clin Neuropathol 9:290-294
26. Curto M, McClatchey AI (2008) Nf2/Merlin: a coordinator of receptor signalling and intercellular contact. Br J Cancer 98:256-262 (Pubitemid 351161230)
27. Ducatman BS, Scheithauer BW (1984) Malignant peripheral nerve sheath tumors with divergent differentiation. Cancer 54:1049-1057 (Pubitemid 14069823)
28. Evans DG, Huson SM, Donnai D, Neary W, Blair V, Newton V, Harris R (1992) A clinical study of type 2 neurofibromatosis. Q J Med 84:603-618 (Pubitemid 23007763)
29. Evans DG, Huson SM, Donnai D, Neary W, Blair V, Teare D, Newton V, Strachan T, Ramsden R, Harris R (1992) A genetic study of type 2 neurofibromatosis in the United Kingdom. I. Prevalence, mutation rate, fitness, and confirmation of maternal transmission effect on severity. J Med Genet 29:841-846 (Pubitemid 23035205)
30. Evans DG, Baser ME, McGaughran J, Sharif S, Howard E, Moran A (2002) Malignant peripheral nerve sheath tumours in neurofibromatosis 1. J Med Genet 39:311-314 (Pubitemid 34526349)
31. Evans DG, Birch JM, Ramsden RT, Sharif S, Baser ME (2006) Malignant transformation and new primary tumours after therapeutic radiation for benign disease: substantial risks in certain tumour prone syndromes. J Med Genet 43:289-294
32. Evans DG, Howard E, Giblin C, Clancy T, Spencer H, Huson SM, Lalloo F (2010) Birth incidence and prevalence of tumor-prone syndromes: estimates from a UK family genetic register service. Am J Med Genet A 152A:327-332
33. Evans GR, Lloyd SK, Ramsden RT (2011) Neurofibromatosis type 2. Adv Otorhinolaryngol 70:91-98
34. Ferner RE, Huson SM, Thomas N, Moss C, Willshaw H, Evans DG, Upadhyaya M, Towers R, Gleeson M, Steiger C, Kirby A (2007) Guidelines for the diagnosis and management of individuals with neurofibromatosis 1. J Med Genet 44:81-88
35. Fossberg TM, Doskeland SO, Ueland PM (1978) Protein kinases in human renal cell carcinoma and renal cortex. A comparison of isozyme distribution and of responsiveness to adenosine 3&prime:5′-cyclic monophosphate. Arch Biochem Biophys 189:272-281
36. Fu YS, Kaye GI, Lattes R (1975) Primary malignant melanocytic tumors of the sympathetic ganglia, with an ultrastructural study of one. Cancer 36:2029-2041
37. Gaujoux S, Tissier F, Groussin L, Libe R, Ragazzon B, Launay P, Audebourg A, Dousset B, Bertagna X, Bertherat J (2008) Wnt/beta-catenin and 3′, 5′-cyclic adenosine 5′-monophosphate/protein kinase A signaling pathways alterations and somatic beta-catenin gene mutations in the progression of adrenocortical tumors. J Clin Endocrinol Metab 93:4135-4140
38. Goutagny S, Kalamarides M (2010) Meningiomas and neurofibromatosis. J Neurooncol 99:341-347
39. Greene EL, Horvath AD, Nesterova M, Giatzakis C, Bossis I, Stratakis CA (2008) In vitro functional studies of naturally occurring pathogenic PRKAR1A mutations that are not subject to nonsense mRNA decay. Hum Mutat 29:633-639 (Pubitemid 351614587)
40. Griffin KJ, Kirschner LS, Matyakhina L, Stergiopoulos S, Robinson-White A, Lenherr S, Weinberg FD, Claflin E, Meoli E, Cho-Chung YS, Stratakis CA (2004) Down-regulation of regulatory subunit type 1A of protein kinase A leads to endocrine and other tumors. Cancer Res 64:8811-8815 (Pubitemid 39665482)
41. Griffin KJ, Kirschner LS, Matyakhina L, Stergiopoulos SG, Robinson-White A, Lenherr SM, Weinberg FD, Claflin ES, Batista D, Bourdeau I, Voutetakis A, Sandrini F, Meoli EM, Bauer AJ, Cho-Chung YS, Bornstein SR, Carney JA, Stratakis CA (2004) A transgenic mouse bearing an antisense construct of regulatory subunit type 1A of protein kinase A develops endocrine and other tumours: comparison with Carney complex and other PRKAR1A induced lesions. J Med Genet 41:923-931 (Pubitemid 40007253)
42. Groussin L, Horvath A, Jullian E, Boikos S, Rene-Corail F, Lefebvre H, Cephise-Velayoudom FL, Vantyghem MC, Chanson P, Conte-Devolx B, Lucas M, Gentil A, Malchoff CD, Tissier F, Carney JA, Bertagna X, Stratakis CA, Bertherat J (2006) A PRKAR1A mutation associated with primary pigmented nodular adrenocortical disease in 12 kindreds. J Clin Endocrinol Metab 91:1943-1949
43. Gujral TS, Singh VK, Jia Z, Mulligan LM (2006) Molecular mechanisms of RET receptor-mediated oncogenesis in multiple endocrine neoplasia 2B. Cancer Res 66:10741-10749 (Pubitemid 44876969)
44. Gutmann DH, Aylsworth A, Carey JC, Korf B, Marks J, Pyeritz RE, Rubenstein A, Viskochil D (1997) The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2. JAMA 278:51-57 (Pubitemid 27274517)
45. Gutmann DH, Collins FS (2002) Neurofibromatosis 1. In: Vogelstein B, Kinzler KW (eds) The genetic basis of human cancer. McGraw-Hill, New York
46. Hadfield KD, Smith MJ, Trump D, Newman WG, Evans DG (2010) SMARCB1 mutations are not a common cause of multiple meningiomas. J Med Genet 47:567-568
47. Handschin JC, Eppenberger U (1979) Altered cellular ratio of type I and type II cyclic AMP-dependent protein kinase in human mammary tumors. FEBS Lett 106:301-304 (Pubitemid 10194224)
48. Hanemann CO, Diebold R, Kaufmann D (2007) Role of NF2 haploinsufficiency in NF2-associated polyneuropathy. Brain Pathol 17:371-376 (Pubitemid 47537594)
49. Horvath A, Boikos S, Giatzakis C, Robinson-White A, Groussin L, Griffin KJ, Stein E, Levine E, Delimpasi G, Hsiao HP, Keil M, Heyerdahl S, Matyakhina L, Libe R, Fratticci A, Kirschner LS, Cramer K, Gaillard RC, Bertagna X, Carney JA, Bertherat J, Bossis I, Stratakis CA (2006) A genome-wide scan identifies mutations in the gene encoding phosphodiesterase 11A4 (PDE11A) in individuals with adrenocortical hyperplasia. Nat Genet 38:794-800 (Pubitemid 43980600)
50. Horvath A, Bossis I, Giatzakis C, Levine E, Weinberg F, Meoli E, Robinson-White A, Siegel J, Soni P, Groussin L, Matyakhina L, Verma S, Remmers E, Nesterova M, Carney JA, Bertherat J, Stratakis CA (2008) Large deletions of the PRKAR1A gene in Carney complex. Clin Cancer Res 14:388-395 (Pubitemid 351226105)
51. Horvath A, Stratakis CA (2009) Carney complex and lentiginosis. Pigment Cell Melanoma Res 22:580-587
52. Hulsebos TJ, Plomp AS, Wolterman RA, Robanus-Maandag EC, Baas F, Wesseling P (2007) Germline mutation of INI1/SMARCB1 in familial schwannomatosis. Am J Hum Genet 80:805-810 (Pubitemid 46564417)
53. Huson SM, Compston DA, Clark P, Harper PS (1989) A genetic study of von Recklinghausen neurofibromatosis in south east Wales. I. Prevalence, fitness, mutation rate, and effect of parental transmission on severity. J Med Genet 26:704-711 (Pubitemid 19270599)
54. Janzer RC, Makek M (1983) Intraoral malignant melanotic schwannoma. Ultrastructural evidence for melanogenesis by Schwann's cells. Arch Pathol Lab Med 107:298-301 (Pubitemid 13093267)
55. Jett K, Friedman JM (2010) Clinical and genetic aspects of neurofibromatosis 1. Genet Med 12:1-11
56. Jouhilahti EM, Peltonen S, Callens T, Jokinen E, Heape AM, Messiaen L, Peltonen J (2011) The development of cutaneous neurofibromas. Am J Pathol 178:500-505
57. Kinderman FS, Kim C, von Daake S, Ma Y, Pham BQ, Spraggon G, Xuong NH, Jennings PA, Taylor SS (2006) A dynamic mechanism for AKAP binding to RII isoforms of cAMP-dependent protein kinase. Mol Cell 24:397-408 (Pubitemid 44647908)
58. Kirschner LS, Carney JA, Pack SD, Taymans SE, Giatzakis C, Cho YS, Cho-Chung YS, Stratakis CA (2000) Mutations of the gene encoding the protein kinase A type I-alpha regulatory subunit in patients with the Carney complex. Nat Genet 26:89-92
59. Kirschner LS, Kusewitt DF, Matyakhina L, Towns WH 2nd, Carney JA, Westphal H, Stratakis CA (2005) A mouse model for the Carney complex tumor syndrome develops neoplasia in cyclic AMP-responsive tissues. Cancer Res 65:4506-4514 (Pubitemid 40740784)
60. Kissil JL, Wilker EW, Johnson KC, Eckman MS, Yaffe MB, Jacks T (2003) Merlin, the product of the Nf2 tumor suppressor gene, is an inhibitor of the p21-activated kinase, Pak1. Mol Cell 12:841-849 (Pubitemid 37352778)
61. Kluwe L, Mautner V, Heinrich B, Dezube R, Jacoby LB, Friedrich RE, MacCollin M (2003) Molecular study of frequency of mosaicism in neurofibromatosis 2 patients with bilateral vestibular schwannomas. J Med Genet 40:109-114 (Pubitemid 36232815)
62. Lallemand D, Curto M, Saotome I, Giovannini M, McClatchey AI (2003) NF2 deficiency promotes tumorigenesis and metastasis by destabilizing adherens junctions. Genes Dev 17:1090-1100 (Pubitemid 36534984)
63. Le LQ, Shipman T, Burns DK, Parada LF (2009) Cell of origin and microenvironment contribution for NF1-associated dermal neurofibromas. Cell Stem Cell 4:453-463
64. Le LQ, Liu C, Shipman T, Chen Z, Suter U, Parada LF (2011) Susceptible stages in Schwann cells for NF1-associated plexiform neurofibroma development. Cancer Res 71:4686-4695
65. Ling BC, Wu J, Miller SJ, Monk KR, Shamekh R, Rizvi TA, Decourten-Myers G, Vogel KS, DeClue JE, Ratner N (2005) Role for the epidermal growth factor receptor in neurofibromatosis- related peripheral nerve tumorigenesis. Cancer Cell 7:65-75 (Pubitemid 40126383)
66. Livesey SA, Kemp BE, Re CA, Partridge NC, Martin TJ (1982) Selective hormonal activation of cyclic AMP-dependent protein kinase isoenzymes in normal and malignant osteoblasts. J Biol Chem 257:14983-14987 (Pubitemid 13164847)
67. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (eds) (2007) WHO classification of tumours of the central nervous system, 4th edn. International Agency for Research on Cancer, Lyon
68. Lu-Emerson C, Plotkin SR (2009) The neurofibromatoses. Part 2: NF2 and schwannomatosis. Rev Neurol Dis 6:E81-E86
69. Lu-Emerson C, Plotkin SR (2009) The neurofibromatoses. Part 1: NF1. Rev Neurol Dis 6:E47-E53
70. MacCollin M, Chiocca EA, Evans DG, Friedman JM, Horvitz R, Jaramillo D, Lev M, Mautner VF, Niimura M, Plotkin SR, Sang CN, Stemmer-Rachamimov A, Roach ES (2005) Diagnostic criteria for schwannomatosis. Neurology 64:1838-1845 (Pubitemid 40800695)
71. Mateus C, Palangie A, Franck N, Groussin L, Bertagna X, Avril MF, Bertherat J, Dupin N (2008) Heterogeneity of skin manifestations in patients with Carney complex. J Am Acad Dermatol 59:801-810
72. Mayes DA, Rizvi TA, Cancelas JA, Kolasinski NT, Ciraolo GM, Stemmer-Rachamimov AO, Ratner N (2011) Perinatal or adult Nf1 inactivation using tamoxifen-inducible PlpCre each cause neurofibroma formation. Cancer Res 71:4675-4685
73. McDaid HM, Cairns MT, Atkinson RJ, McAleer S, Harkin DP, Gilmore P, Johnston PG (1999) Increased expression of the RIalpha subunit of the cAMP-dependent protein kinase A is associated with advanced stage ovarian cancer. Br J Cancer 79:933-939 (Pubitemid 29082129)
74. Meoli E, Bossis I, Cazabat L, Mavrakis M, Horvath A, Stergiopoulos S, Shiferaw ML, Fumey G, Perlemoine K, Muchow M, Robinson-White A, Weinberg F, Nesterova M, Patronas Y, Groussin L, Bertherat J, Stratakis CA (2008) Protein kinase A effects of an expressed PRKAR1A mutation associated with aggressive tumors. Cancer Res 68:3133-3141
75. Merel P, Hoang-Xuan K, Sanson M, Bijlsma E, Rouleau G, Laurent-Puig P, Pulst S, Baser M, Lenoir G, Sterkers JM et al (1995) Screening for germ-line mutations in the NF2 gene. Genes Chromosomes Cancer 12:117-127
76. Messiaen L, Yao S, Brems H, Callens T, Sathienkijkanchai A, Denayer E, Spencer E, Arn P, Babovic-Vuksanovic D, Bay C, Bobele G, Cohen BH, Escobar L, Eunpu D, Grebe T, Greenstein R, Hachen R, Irons M, Kronn D, Lemire E, Leppig K, Lim C, McDonald M, Narayanan V, Pearn A, Pedersen R, Powell B, Shapiro LR, Skidmore D, Tegay D, Thiese H, Zackai EH, Vijzelaar R, Taniguchi K, Ayada T, Okamoto F, Yoshimura A, Parret A, Korf B, Legius E (2009) Clinical and mutational spectrum of neurofibromatosis type 1-like syndrome. JAMA 302:2111-2118
77. Moyhuddin A, Baser ME, Watson C, Purcell S, Ramsden RT, Heiberg A, Wallace AJ, Evans DG (2003) Somatic mosaicism in neurofibromatosis 2: prevalence and risk of disease transmission to offspring. J Med Genet 40:459-463 (Pubitemid 36760665)
78. Mulvihill JJ, Parry DM, Sherman JL, Pikus A, Kaiser-Kupfer MI, Eldridge R (1990) NIH conference. Neurofibromatosis 1 (Recklinghausen disease) and neurofibromatosis 2 (bilateral acoustic neurofibromatosis). An update. Ann Intern Med 113:39-52 (Pubitemid 20196630)
79. Nakajima F, Imashuku S, Wilimas J, Champion JE, Green AA (1984) Distribution and properties of type I and type II binding proteins in the cyclic adenosine 3′:5′-monophosphate-dependent protein kinase system in Wilms' tumor. Cancer Res 44:5182-5187 (Pubitemid 15204486)
80. Papageorgiou T, Stratakis CA (2002) Ovarian tumors associated with multiple endocrine neoplasias and related syndromes (Carney complex, Peutz-Jeghers syndrome, von Hippel-Lindau disease, Cowden's disease). Int J Gynecol Cancer 12:337-347 (Pubitemid 34839831)
81. Patil S, Perry A, Maccollin M, Dong S, Betensky RA, Yeh TH, Gutmann DH, Stemmer-Rachamimov AO (2008) Immunohistochemical analysis supports a role for INI1/SMARCB1 in hereditary forms of schwannomas, but not in solitary, sporadic schwannomas. Brain Pathol 18:517-519
82. Perry A, Roth KA, Banerjee R, Fuller CE, Gutmann DH (2001) NF1 deletions in S-100 protein-positive and negative cells of sporadic and neurofibromatosis 1 (NF1)-associated plexiform neurofibromas and malignant peripheral nerve sheath tumors. Am J Pathol 159:57-61 (Pubitemid 33704192)
83. Perry A, Kunz SN, Fuller CE, Banerjee R, Marley EF, Liapis H, Watson MA, Gutmann DH (2002) Differential NF1, p16, and EGFR patterns by interphase cytogenetics (FISH) in malignant peripheral nerve sheath tumor (MPNST) and morphologically similar spindle cell neoplasms. J Neuropathol Exp Neurol 61:702-709 (Pubitemid 34851773)
84. Razzaque MA, Nishizawa T, Komoike Y, Yagi H, Furutani M, Amo R, Kamisago M, Momma K, Katayama H, Nakagawa M, Fujiwara Y, Matsushima M, Mizuno K, Tokuyama M, Hirota H, Muneuchi J, Higashinakagawa T, Matsuoka R (2007) Germline gain-of-function mutations in RAF1 cause Noonan syndrome. Nat Genet 39:1013-1017 (Pubitemid 47185179)
85. Reith JD, Goldblum JR (1996) Multiple cutaneous plexiform schwannomas. Report of a case and review of the literature with particular reference to the association with types 1 and 2 neurofibromatosis and schwannomatosis. Arch Pathol Lab Med 120:399-401 (Pubitemid 26113418)
86. Rhodes AR, Silverman RA, Harrist TJ, Perez-Atayde AR (1984) Mucocutaneous lentigines, cardiomucocutaneous myxomas, and multiple blue nevi: the "LAMB" syndrome. J Am Acad Dermatol 10:72-82 (Pubitemid 14222032)
87. Riccardi VM (1992) Neurofibromatosis: Phenotpe, Natural History, and Pathogenesis, Second edn. The Johns Hopkins University Press, Baltimore
88. Robinson-White A, Meoli E, Stergiopoulos S, Horvath A, Boikos S, Bossis I, Stratakis CA (2006) PRKAR1A Mutations and protein kinase A interactions with other signaling pathways in the adrenal cortex. J Clin Endocrinol Metab 91:2380-2388 (Pubitemid 43855031)
89. Rodriguez FJ, Scheithauer BW, Abell-Aleff PC, Elamin E, Erlandson RA (2007) Low grade malignant peripheral nerve sheath tumor with smooth muscle differentiation. Acta Neuropathol 113:705-709 (Pubitemid 46863906)
90. Rodriguez FJ, Scheithauer BW, George D, Midha R, MacCollin M, Stemmer-Rachamimov AO (2011) Superficial neurofibromas in the setting of schwannomatosis: nosologic implications. Acta Neuropathol 121:663-668
91. Rodriguez FJ, Folpe AL, Giannini C, Perry A (2012) pathology of peripheral nerve sheath tumors: diagnostic overview and update on selected diagnostic problems. Acta Neuropathol
92. Rothenbuhler A, Stratakis CA (2010) Clinical and molecular genetics of Carney complex. Best Pract Res Clin Endocrinol Metab 24:389-399
93. Rouleau GA, Merel P, Lutchman M, Sanson M, Zucman J, Marineau C, Hoang-Xuan K, Demczuk S, Desmaze C, Plougastel B et al (1993) Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2. Nature 363:515-521 (Pubitemid 23186636)
94. Roytta M, Elfversson J, Kalimo H (1988) Intraspinal pigmented schwannoma with malignant progression. Acta Neurochir (Wien) 95:147-154 (Pubitemid 19024322)
95. Sandrini F, Stratakis C (2003) Clinical and molecular genetics of Carney complex. Mol Genet Metab 78:83-92 (Pubitemid 36279622)
96. Schaffer JV, Kamino H, Witkiewicz A, McNiff JM, Orlow SJ (2006) Mucocutaneous neuromas: an underrecognized manifestation of PTEN hamartoma-tumor syndrome. Arch Dermatol 142:625-632 (Pubitemid 43727554)
97. Scheithauer BW, Woodruff JM, Erlandson RA (1997) Tumors of the Peripheral Nervous System. Armed Forces Institute of Pathology, Washington D.C
98. Scott JD (1991) Cyclic nucleotide-dependent protein kinases. Pharmacol Ther 50:123-145
99. Selvanathan SK, Shenton A, Ferner R, Wallace AJ, Huson SM, Ramsden RT, Evans DG (2010) Further genotype-phenotype correlations in neurofibromatosis 2. Clin Genet 77:163-170
100. Sestini R, Bacci C, Provenzano A, Genuardi M, Papi L (2008) Evidence of a four-hit mechanism involving SMARCB1 and NF2 in schwannomatosis-associated schwannomas. Hum Mutat 29:227-231 (Pubitemid 351240594)
101. Shabb JB (2001) Physiological substrates of cAMP-dependent protein kinase. Chem Rev 101:2381-2411
102. Stratakis CA, Carney JA, Lin JP, Papanicolaou DA, Karl M, Kastner DL, Pras E, Chrousos GP (1996) Carney complex, a familial multiple neoplasia and lentiginosis syndrome. Analysis of 11 kindreds and linkage to the short arm of chromosome 2. J Clin Invest 97:699-705 (Pubitemid 26057088)
103. Stratakis CA, Courcoutsakis NA, Abati A, Filie A, Doppman JL, Carney JA, Shawker T (1997) Thyroid gland abnormalities in patients with the syndrome of spotty skin pigmentation, myxomas, endocrine overactivity, and schwannomas (Carney complex). J Clin Endocrinol Metab 82:2037-2043 (Pubitemid 27287558)
104. Stratakis CA, Kirschner LS, Carney JA (1998) Carney complex: diagnosis and management of the complex of spotty skin pigmentation, myxomas, endocrine overactivity, and schwannomas. Am J Med Genet 80:183-185 (Pubitemid 28485703)
105. Stratakis CA (2000) Genetics of Peutz-Jeghers syndrome, Carney complex and other familial lentiginoses. Horm Res 54:334-343
106. Stratakis CA, Papageorgiou T, Premkumar A, Pack S, Kirschner LS, Taymans SE, Zhuang Z, Oelkers WH, Carney JA (2000) Ovarian lesions in Carney complex: clinical genetics and possible predisposition to malignancy. J Clin Endocrinol Metab 85:4359-4366 (Pubitemid 32055399)
107. Stratakis CA, Kirschner LS, Carney JA (2001) Clinical and molecular features of the Carney complex: diagnostic criteria and recommendations for patient evaluation. J Clin Endocrinol Metab 86:4041-4046 (Pubitemid 32848510)
108. Tadjine M, Lampron A, Ouadi L, Horvath A, Stratakis CA, Bourdeau I (2008) Detection of somatic beta-catenin mutations in primary pigmented nodular adrenocortical disease (PPNAD). Clin Endocrinol (Oxf) 69:367-373
109. Takahashi M, Cooper GM (1987) ret transforming gene encodes a fusion protein homologous to tyrosine kinases. Mol Cell Biol 7:1378-1385 (Pubitemid 17045226)
110. Tasken K, Skalhegg BS, Tasken KA, Solberg R, Knutsen HK, Levy FO, Sandberg M, Orstavik S, Larsen T, Johansen AK, Vang T, Schrader HP, Reinton NT, Torgersen KM, Hansson V, Jahnsen T (1997) Structure, function, and regulation of human cAMP-dependent protein kinases. Adv Second Messenger Phosphoprot Res 31:191-204
111. Trofatter JA, MacCollin MM, Rutter JL, Murrell JR, Duyao MP, Parry DM, Eldridge R, Kley N, Menon AG, Pulaski K et al (1993) A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor. Cell 72:791-800 (Pubitemid 23093886)
112. Val-Bernal JF, Figols J, Vazquez-Barquero A (1995) Cutaneous plexiform schwannoma associated with neurofibromatosis type 2. Cancer 76:1181-1186
113. Veugelers M, Wilkes D, Burton K, McDermott DA, Song Y, Goldstein MM, La Perle K, Vaughan CJ, O'Hagan A, Bennett KR, Meyer BJ, Legius E, Karttunen M, Norio R, Kaariainen H, Lavyne M, Neau JP, Richter G, Kirali K, Farnsworth A, Stapleton K, Morelli P, Takanashi Y, Bamforth JS, Eitelberger F, Noszian I, Manfroi W, Powers J, Mochizuki Y, Imai T, Ko GT, Driscoll DA, Goldmuntz E, Edelberg JM, Collins A, Eccles D, Irvine AD, McKnight GS, Basson CT (2004) Comparative PRKAR1A genotype-phenotype analyses in humans with Carney complex and prkar1a haploinsufficient mice. Proc Natl Acad Sci USA 101:14222-14227 (Pubitemid 39305057)
114. Wallace MR, Marchuk DA, Andersen LB, Letcher R, Odeh HM, Saulino AM, Fountain JW, Brereton A, Nicholson J, Mitchell AL et al (1990) Type 1 neurofibromatosis gene: identification of a large transcript disrupted in three NF1 patients. Science 249:181-186
115. Warrington NM, Gianino SM, Jackson E, Goldhoff P, Garbow JR, Piwnica-Worms D, Gutmann DH, Rubin JB (2010) Cyclic AMP suppression is sufficient to induce gliomagenesis in a mouse model of neurofibromatosis-1. Cancer Res 70:5717-5727
116. Watson DM, Hawkins RA, Bundred NJ, Stewart HJ, Miller WR (1987) Tumour cyclic AMP binding proteins and endocrine responsiveness in patients with inoperable breast cancer. Br J Cancer 56:141-142 (Pubitemid 17155526)
117. Woodruff JM, Christensen WN (1993) Glandular peripheral nerve sheath tumors. Cancer 72:3618-3628 (Pubitemid 24000596)
118. Woodruff JM, Perino G (1994) Non-germ-cell or teratomatous malignant tumors showing additional rhabdomyoblastic differentiation, with emphasis on the malignant Triton tumor. Semin Diagn Pathol 11:69-81 (Pubitemid 24092137)
119. Woodruff JM (1999) Pathology of tumors of the peripheral nerve sheath in type 1 neurofibromatosis. Am J Med Genet 89:23-30
120. Wu J, Williams JP, Rizvi TA, Kordich JJ, Witte D, Meijer D, Stemmer-Rachamimov AO, Cancelas JA, Ratner N (2008) Plexiform and dermal neurofibromas and pigmentation are caused by Nf1 loss in desert hedgehog-expressing cells. Cancer Cell 13:105-116 (Pubitemid 351163159)
121. Yang FC, Ingram DA, Chen S, Zhu Y, Yuan J, Li X, Yang X, Knowles S, Horn W, Li Y, Zhang S, Yang Y, Vakili ST, Yu M, Burns D, Robertson K, Hutchins G, Parada LF, Clapp DW (2008) Nf1-dependent tumors require a microenvironment containing Nf1± and c-kit-dependent bone marrow. Cell 135:437-448
122. Yin Z, Jones GN, Towns WH 2nd, Zhang X, Abel ED, Binkley PF, Jarjoura D, Kirschner LS (2008) Heart-specific ablation of Prkar1a causes failure of heart development and myxomagenesis. Circulation 117:1414-1422 (Pubitemid 351501494)
123. Yin Z, Williams-Simons L, Parlow AF, Asa S, Kirschner LS (2008) Pituitary-specific knockout of the Carney complex gene Prkar1a leads to pituitary tumorigenesis. Mol Endocrinol 22:380-387 (Pubitemid 351185937)
124. Yu J, Deshmukh H, Payton JE, Dunham C, Scheithauer BW, Tihan T, Prayson RA, Guha A, Bridge JA, Ferner RE, Lindberg GM, Gutmann RJ, Emnett RJ, Salavaggione L, Gutmann DH, Nagarajan R, Watson MA, Perry A (2011) Array-based comparative genomic hybridization identifies CDK4 and FOXM1 alterations as independent predictors of survival in malignant peripheral nerve sheath tumor. Clin Cancer Res 17:1924-1934
125. Zheng H, Chang L, Patel N, Yang J, Lowe L, Burns DK, Zhu Y (2008) Induction of abnormal proliferation by nonmyelinating schwann cells triggers neurofibroma formation. Cancer Cell 13:117-128 (Pubitemid 351163161)