Primary melanocytic tumors of the central nervous system: A review with focus on molecular aspects

Brain Pathology

Volumn 25, Issue 2, 2015, Pages 209-226

  Küsters Vandevelde, Heidi V N ^a   Küsters, Benno ^b,c   Van Engen Van Grunsven, Adriana C H ^b   Groenen, Patricia J T A ^b   Wesseling, Pieter ^a,b,d   Blokx, Willeke A M ^b  

^a CANISIUS WILHELMINA HOSPITAL   (Netherlands)

^b RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

^c MAASTRICHT UNIVERSITY MEDICAL CENTER   (Netherlands)

^d VU UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

brain; central nervous system; GNA11; GNAQ; leptomeningeal melanocytic neoplasms; melanocytoma; melanoma; melanotic schwannoma; metastasis; molecular; mosaic RASopathy; neurocutaneous melanosis; NRAS

Indexed keywords

CANCER GENETICS; CANCER GRADING; CANCER PATIENT; CENTRAL NERVOUS SYSTEM TUMOR; CHILDHOOD CANCER; CLINICAL FEATURE; DIFFERENTIAL DIAGNOSIS; GENE MUTATION; GENETIC ASSOCIATION; GNA11 GENE; GNAQ GENE; HUMAN; MELANOCYTIC NEVUS; MELANOCYTOSIS; MELANOMA; MOLECULAR PATHOLOGY; MOLECULARLY TARGETED THERAPY; MUTATIONAL ANALYSIS; ONCOGENE N RAS; PHAKOMATOSIS; PRIMARY MELANOCYTIC TUMORS OF THE CENTRAL NERVOUS SYSTEM; PRIMARY TUMOR; RARE DISEASE; REVIEW; TUMOR CLASSIFICATION; TUMOR DIAGNOSIS; TUMOR GENE; ANIMAL; GENETICS; MELANOCYTE; MENINGIOMA; METABOLISM; MUTATION; SIGNAL TRANSDUCTION;

GNA11 PROTEIN, HUMAN; GNAQ PROTEIN, HUMAN; GUANINE NUCLEOTIDE BINDING PROTEIN ALPHA SUBUNIT; GUANOSINE TRIPHOSPHATASE; MEMBRANE PROTEIN; NRAS PROTEIN, HUMAN;

ANIMALS; CENTRAL NERVOUS SYSTEM NEOPLASMS; GTP PHOSPHOHYDROLASES; GTP-BINDING PROTEIN ALPHA SUBUNITS; HUMANS; MELANOCYTES; MELANOMA; MEMBRANE PROTEINS; MENINGEAL NEOPLASMS; MUTATION; SIGNAL TRANSDUCTION;

EID: 84922672077     PISSN: 10156305     EISSN: 17503639     Source Type: Journal    
DOI: 10.1111/bpa.12241     Document Type: Review

References (148)

1. Ackermann J, Frutschi M, Kaloulis K, McKee T, Trumpp A, Beermann F, (2005) Metastasizing melanoma formation caused by expression of activated N-RasQ61K on an INK4a-deficient background. Cancer Res 65: 4005-4011.
2. Alla P, Carsuzaa F, Fesselet J, Muyard B, Carloz E, Piersecki MD, et al (1998) Blue nevus of the scalp associated with a meningeal melanocytoma. Ann Dermatol Venereol 125: 129-131.
3. Allcutt D, Michowiz S, Weitzman S, Becker L, Blaser S, Hoffman HJ, et al (1993) Primary leptomeningeal melanoma: an unusually aggressive tumor in childhood. Neurosurgery 32: 721-729.
4. Ambrosini G, Musi E, Ho AL, de Stanchina E, Schwartz GK, (2013) Inhibition of mutant GNAQ signaling in uveal melanoma induces AMPK-dependent autophagic cell death. Mol Cancer Ther 12: 768-776.
5. Ambrosini G, Pratilas CA, Qin LX, Tadi M, Surriga O, Carvajal RD, Schwartz GK, (2012) Identification of unique MEK-dependent genes in GNAQ mutant uveal melanoma involved in cell growth, tumor cell invasion, and MEK resistance. Clin Cancer Res 18: 3552-3561.
6. Antonescu CR, Scheithauer BW, Woodruff JM, (2013) Tumors of the peripheral nervous system. In: AFIP Atlas of Tumor Pathology. American Registry of Pathology Press (ed.), American Registry of Pathology: Silver Spring, Maryland.
7. Aoki H, Yamada Y, Hara A, Kunisada T, (2009) Two distinct types of mouse melanocyte: differential signaling requirement for the maintenance of non-cutaneous and dermal versus epidermal melanocytes. Development 136: 2511-2521.
8. Arias M, Alberte-Woodward M, Arias S, Dapena D, Prieto A, Suarez-Penaranda JM, (2011) Primary malignant meningeal melanomatosis: a clinical, radiological and pathologic case study. Acta Neurol Belg 111: 228-231.
9. Ascierto PA, Schadendorf D, Berking C, Agarwala SS, van Herpen CM, Queirolo P, et al (2013) MEK162 for patients with advanced melanoma harbouring NRAS or Val600 BRAF mutations: a non-randomised, open-label phase 2 study. Lancet Oncol 14: 249-256.
10. Balmaceda CM, Fetell MR, O'Brien JL, Housepian EH, (1993) Nevus of Ota and leptomeningeal melanocytic lesions. Neurology 43: 381-386.
11. Bauer J, Curtin JA, Pinkel D, Bastian BC, (2007) Congenital melanocytic nevi frequently harbor NRAS mutations but no BRAF mutations. J Invest Dermatol 127: 179-182.
12. Bauer J, Kilic E, Vaarwater J, Bastian BC, Garbe C, de Klein A, (2009) Oncogenic GNAQ mutations are not correlated with disease-free survival in uveal melanoma. Br J Cancer 101: 813-815.
13. Beadling C, Jacobson-Dunlop E, Hodi FS, Le C, Warrick A, Patterson J, et al (2008) KIT gene mutations and copy number in melanoma subtypes. Clin Cancer Res 14: 6821-6828.
14. Bergdahl L, Boquist L, Liliequist B, Thulin CA, Tovi D, (1972) Primary malignant melanoma of the central nervous system. A report of 10 cases. Acta Neurochir 26: 139-149.
15. Bertherat J, Horvath A, Groussin L, Grabar S, Boikos S, Cazabat L, et al (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.
16. Brat DJ, Giannini C, Scheithauer BW, Burger PC, (1999) Primary melanocytic neoplasms of the central nervous systems. Am J Surg Pathol 23: 745-754.
17. Brat DJ, Perry A, (2007) Melanocytic lesions. Chapter 10. In: WHO Classification of Tumours of the Central Nervous System., DN Louis, H Ohgaki, OD Wiestler, WK Cavenee, (eds), pp. 181-183. International Agency for Research on Cancer: Lyon.
18. Brunsvig KL, Zenobi M, Rilliet B, El Hassani Y, de Haller R, Ansari M, et al (2011) Primary leptomeningeal melanocytosis in a 10-year-old girl: a challenging diagnosis with a poor prognosis. J Child Neurol 26: 1444-1448.
19. Bullard DE, Cox EB, Seigler HF, (1981) Central nervous system metastases in malignant melanoma. Neurosurgery 8: 26-30.
20. Bydon A, Gutierrez JA, Mahmood A, (2003) Meningeal melanocytoma: an aggressive course for a benign tumor. J Neurooncol 64: 259-263.
21. 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.
22. Carvajal RD, Antonescu CR, Wolchok JD, Chapman PB, Roman RA, Teitcher J, et al (2011) KIT as a therapeutic target in metastatic melanoma. JAMA 305: 2327-2334.
23. Carvajal RD, Sosman JA, Quevedo JF, Milhem MM, Joshua AM, Kudchadkar RR, et al (2014) Effect of selumetinib vs chemotherapy on progression-free survival in uveal melanoma: a randomized clinical trial. JAMA 311: 2397-2405.
24. Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, et al (2011) Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 364: 2507-2516.
25. Chen X, Wu Q, Tan L, Porter D, Jager MJ, Emery C, Bastian BC, (2013) Combined PKC and MEK inhibition in uveal melanoma with GNAQ and GNA11 mutations. Oncogene 33: 4724-4734.
26. Chin L, Pomerantz J, Polsky D, Jacobson M, Cohen C, Cordon-Cardo C, et al (1997) Cooperative effects of INK4a and ras in melanoma susceptibility in vivo. Genes Dev 11: 2822-2834.
27. Cohn-Cedermark G, Mansson-Brahme E, Rutqvist LE, Larsson O, Johansson H, Ringborg U, (1998) Central nervous system metastases of cutaneous malignant melanoma-a population-based study. Acta Oncol 37: 463-470.
28. Cornejo KM, Hutchinson L, Cosar EF, Smith T, Tomaszewicz K, Dresser K, Deng A, (2013) Is it a primary or metastatic melanocytic neoplasm of the central nervous system?: a molecular based approach. Pathol Int 63: 559-564.
29. Cruz F 3rd, Rubin BP, Wilson D, Town A, Schroeder A, Haley A, et al (2003) Absence of BRAF and NRAS mutations in uveal melanoma. Cancer Res 63: 5761-5766.
30. Curtin JA, Busam K, Pinkel D, Bastian BC, (2006) Somatic activation of KIT in distinct subtypes of melanoma. J Clin Oncol 24: 4340-4346.
31. Curtin JA, Fridlyand J, Kageshita T, Patel HN, Busam KJ, Kutzner H, et al (2005) Distinct sets of genetic alterations in melanoma. N Engl J Med 353: 2135-2147.
32. Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, et al (2002) Mutations of the BRAF gene in human cancer. Nature 417: 949-954.
33. Dessars B, De Raeve LE, Morandini R, Lefort A, El Housni H, Ghanem GE, et al (2009) Genotypic and gene expression studies in congenital melanocytic nevi: insight into initial steps of melanotumorigenesis. J Invest Dermatol 129: 139-147.
34. Domingues MJ, Larue L, Bonaventure J, (2013) Migration of melanocytic lineage-derived cells. Med Sci 29: 287-292.
35. Dono M, Angelini G, Cecconi M, Amaro A, Esposito AI, Mirisola V, et al (2014) Mutation frequencies of GNAQ, GNA11, BAP1, SF3B1, EIF1AX and TERT in uveal melanoma: detection of an activating mutation in the TERT gene promoter in a single case of uveal melanoma. Br J Cancer 110: 1058-1065.
36. Dubbink HJ, Deans ZC, Tops BB, van Kemenade FJ, Koljenovic S, van Krieken HJ, et al (2014) Next generation diagnostic molecular pathology: critical appraisal of quality assurance in Europe. Mol Oncol 8: 830-839.
37. Edlundh-Rose E, Egyhazi S, Omholt K, Mansson-Brahme E, Platz A, Hansson J, Lundeberg J, (2006) NRAS and BRAF mutations in melanoma tumours in relation to clinical characteristics: a study based on mutation screening by pyrosequencing. Melanoma Res 16: 471-478.
38. van Engen-van Grunsven IA, Kusters-Vandevelde HVN, Groenen PJTA, Blokx WAM, (2014) Update on molecular pathology of cutaneous melanocytic lesions: what is new in diagnosis and molecular testing for treatment? Front Med 1: 39. doi: 10.3389/fmed.2014.00039.
39. Eun SS, Kim HS, Lee SH, Liu WC, Lee JH, (2011) Spinal meningeal melanocytoma in the S-1 nerve root sheath with paraspinal extension mimicking schwannoma. World Neurosurg 75: 303-306.
40. von Euw E, Atefi M, Attar N, Chu C, Zachariah S, Burgess BL, et al (2012) Antitumor effects of the investigational selective MEK inhibitor TAK733 against cutaneous and uveal melanoma cell lines. Mol Cancer 11: 22. doi: 10.1186/1476-4598-11-22.
41. Fecher LA, Amaravadi RK, Flaherty KT, (2008) The MAPK pathway in melanoma. Curr Opin Oncol 20: 183-189.
42. Feng X, Degese MS, Iglesias-Bartolome R, Vaque JP, Molinolo AA, Rodrigues M, et al (2014) Hippo-independent activation of YAP by the GNAQ uveal melanoma oncogene through a trio-regulated rho GTPase signaling circuitry. Cancer Cell 25: 831-845.
43. Fernandez-Medarde A, Santos E, (2011) Ras in cancer and developmental diseases. Genes Cancer 2: 344-358.
44. Fuld AD, Speck ME, Harris BT, Simmons NE, Corless CL, Tsongalis GJ, et al (2011) Primary melanoma of the spinal cord: a case report, molecular footprint, and review of the literature. J Clin Oncol 29: 499-502.
45. Gessi M, Hammes J, Lauriola L, Dorner E, Kirfel J, Kristiansen G, et al (2012) GNA11 and N-RAS mutations: alternatives for MAPK pathway activating GNAQ mutations in primary melanocytic tumours of the central nervous system. Neuropathol Appl Neurobiol 39: 417-425.
46. Gessi M, van de Nes J, Griewank K, Barresi V, Buckland ME, Kirfel J, et al (2014) Absence of TERT promoter mutations in primary melanocytic tumours of the central nervous system. Neuropathol Appl Neurobiol 40: 794-797.
47. Goldgeier MH, Klein LE, Klein-Angerer S, Moellmann G, Nordlund JJ, (1984) The distribution of melanocytes in the leptomeninges of the human brain. J Invest Dermatol 82: 235-238.
48. Greaves WO, Verma S, Patel KP, Davies MA, Barkoh BA, Galbincea JM, et al (2013) Frequency and spectrum of BRAF mutations in a retrospective, single-institution study of 1112 cases of melanoma. J Mol Diagn 15: 220-226.
49. Greco Crasto S, Soffietti R, Bradac GB, Boldorini R, (2001) Primitive cerebral melanoma: case report and review of the literature. Surg Neurol 55: 163-168.
50. Guo J, Si L, Kong Y, Flaherty KT, Xu X, Zhu Y, et al (2011) Phase II, open-label, single-arm trial of imatinib mesylate in patients with metastatic melanoma harboring c-Kit mutation or amplification. J Clin Oncol 29: 2904-2909.
51. Hafner C, Groesser L, (2013) Mosaic RASopathies. Cell Cycle 12: 43-50.
52. Harbour JW, Onken MD, Roberson ED, Duan S, Cao L, Worley LA, et al (2010) Frequent mutation of BAP1 in metastasizing uveal melanomas. Science 330: 1410-1413.
53. Hawes BE, van Biesen T, Koch WJ, Luttrell LM, Lefkowitz RJ, (1995) Distinct pathways of Gi- and Gq-mediated mitogen-activated protein kinase activation. J Biol Chem 270: 17148-17153.
54. Helseth A, Helseth E, Unsgaard G, (1989) Primary meningeal melanoma. Acta Oncol 28: 103-104.
55. Ho AL, Musi E, Ambrosini G, Nair JS, Deraje Vasudeva S, de Stanchina E, Schwartz GK, (2012) Impact of combined mTOR and MEK inhibition in uveal melanoma is driven by tumor genotype. PLoS ONE 7: e40439.
56. Hodi FS, Corless CL, Giobbie-Hurder A, Fletcher JA, Zhu M, Marino-Enriquez A, et al (2013) Imatinib for melanomas harboring mutationally activated or amplified KIT arising on mucosal, acral, and chronically sun-damaged skin. J Clin Oncol 31: 3182-3190.
57. Holbrook KA, Underwood RA, Vogel AM, Gown AM, Kimball H, (1989) The appearance, density and distribution of melanocytes in human embryonic and fetal skin revealed by the anti-melanoma monoclonal antibody, HMB-45. Anat Embryol (Berl) 180: 443-455.
58. Horvath A, Bertherat J, Groussin L, Guillaud-Bataille M, Tsang K, Cazabat L, et al (2010) Mutations and polymorphisms in the gene encoding regulatory subunit type 1-alpha of protein kinase A (PRKAR1A): an update. Hum Mutat 31: 369-379.
59. Huang FW, Hodis E, Xu MJ, Kryukov GV, Chin L, Garraway LA, (2013) Highly recurrent TERT promoter mutations in human melanoma. Science 339: 957-959.
60. Huang HY, Park N, Erlandson RA, Antonescu CR, (2004) Immunohistochemical and ultrastructural comparative study of external lamina structure in 31 cases of cellular, classical, and melanotic schwannomas. Appl Immunohistochem Mol Morphol 12: 50-58.
61. Hubbard KB, Hepler JR, (2006) Cell signalling diversity of the Gqalpha family of heterotrimeric G proteins. Cell Signal 18: 135-150.
62. Hurowitz EH, Melnyk JM, Chen YJ, Kouros-Mehr H, Simon MI, Shizuya H, (2000) Genomic characterization of the human heterotrimeric G protein alpha, beta, and gamma subunit genes. DNA Res 7: 111-120.
63. Hwang HW, Pavan WJ, (2010) Melanocytes don't always take the high road. Pigment Cell Melanoma Res 23: 11-13.
64. Jiveskog S, Ragnarsson-Olding B, Platz A, Ringborg U, (1998) N-ras mutations are common in melanomas from sun-exposed skin of humans but rare in mucosal membranes or unexposed skin. J Invest Dermatol 111: 757-761.
65. Kadonaga JN, Frieden IJ, (1991) Neurocutaneous melanosis: definition and review of the literature. J Am Acad Dermatol 24: 747-755.
66. Kelleher FC, McArthur GA, (2012) Targeting NRAS in melanoma. Cancer J 18: 132-136.
67. Khalili JS, Yu X, Wang J, Hayes BC, Davies MA, Lizee G, et al (2012) Combination small molecule MEK and PI3K inhibition enhances uveal melanoma cell death in a mutant GNAQ- and GNA11-dependent manner. Clin Cancer Res 18: 4345-4355.
68. Kim CY, Kim DW, Kim K, Curry J, Torres-Cabala C, Patel S, (2014) GNAQ mutation in a patient with metastatic mucosal melanoma. BMC Cancer 14: 516. doi: 10.1186/1471-2407-14-516.
69. Kinsler VA, Paine SM, Anderson GW, Wijesekara DS, Sebire NJ, Chong WK, et al (2012) Neuropathology of neurocutaneous melanosis: histological foci of melanotic neurones and glia may be undetectable on MRI. Acta Neuropathol 123: 453-456.
70. Kinsler VA, Thomas AC, Ishida M, Bulstrode NW, Loughlin S, Hing S, et al (2013) Multiple congenital melanocytic nevi and neurocutaneous melanosis are caused by postzygotic mutations in codon 61 of NRAS. J Invest Dermatol 133: 2229-2236.
71. Koelsche C, Hovestadt V, Jones D, Capper D, Sturm D, Sahm F, et al (2014) Melanotic tumors of the nervous system are characterized by distinct mutational, chromosomal and epigenomic profiles. Brain Pathol doi: 10.1111/bpa.12228.
72. Koenigsmann M, Jautzke G, Unger M, Theallier-Janko A, Wiegel T, Stoltenburg-Didinger G, (2002) June 2002: 57-year-old male with leptomeningeal and liver tumors. Brain Pathol 12: 519-521.
73. Kong Y, Krauthammer M, Halaban R, (2014) Rare SF3B1 R625 mutations in cutaneous melanoma. Melanoma Res 24: 332-334.
74. Koopmans AE, Vaarwater J, Paridaens D, Naus NC, Kilic E, de Klein A, (2013) Patient survival in uveal melanoma is not affected by oncogenic mutations in GNAQ and GNA11. Br J Cancer 109: 493-496.
75. Kusters-Vandevelde HV, van Engen-van Grunsven IA, Coupland SE, Lake S, Rijntjes J, Pfundt R, et al (2014) Mutations in G protein encoding genes and chromosomal alterations in primary leptomeningeal melanocytic neoplasms. Pathol Oncol Res doi: 10.1007/s12253-014-9841-3.
76. Kusters-Vandevelde HV, van Engen-van Grunsven IA, Kusters B, van Dijk MR, Groenen PJ, Wesseling P, Blokx WA, (2010) Improved discrimination of melanotic schwannoma from melanocytic lesions by combined morphological and GNAQ mutational analysis. Acta Neuropathol 120: 755-764.
77. Kusters-Vandevelde HV, Klaasen A, Kusters B, Groenen PJ, van Engen-van Grunsven IA, van Dijk MR, et al (2009) Activating mutations of the GNAQ gene: a frequent event in primary melanocytic neoplasms of the central nervous system. Acta Neuropathol 119: 317-323.
78. Kusters-Vandevelde HV, Willemsen AE, Groenen PJ, Kusters B, Lammens M, Wesseling P, et al (2014) Experimental treatment of NRAS-mutated neurocutaneous melanocytosis with MEK162, a MEK-inhibitor. Acta Neuropathol Commun 2: 41. doi: 10.1186/2051-5960-2-41.
79. Langer R, Becker K, Feith M, Friess H, Hofler H, Keller G, (2011) Genetic aberrations in primary esophageal melanomas: molecular analysis of c-KIT, PDGFR, KRAS, NRAS and BRAF in a series of 10 cases. Mod Pathol 24: 495-501.
80. Le Douarin NMKC, (1999) The Neural Crest. Cambridge University Press: Cambridge.
81. Lee JH, Choi JW, Kim YS, (2011) Frequencies of BRAF and NRAS mutations are different in histological types and sites of origin of cutaneous melanoma: a meta-analysis. Br J Dermatol 164: 776-784.
82. Leopold JG, Richards DB, (1968) The interrelationship of blue and common naevi. J Pathol Bacteriol 95: 37-46.
83. Louis DN, Perry A, Burger P, Ellison DW, Reifenberger G, von Deimling A, et al (2014) International Society of Neuropathology - Haarlem consensus guidelines for nervous system tumor classification and grading. Brain Pathol 24: 429-435.
84. Makin GW, Eden OB, Lashford LS, Moppett J, Gerrard MP, Davies HA, et al (1999) Leptomeningeal melanoma in childhood. Cancer 86: 878-886.
85. Malaponte G, Libra M, Gangemi P, Bevelacqua V, Mangano K, D'Amico F, et al (2006) Detection of BRAF gene mutation in primary choroidal melanoma tissue. Cancer Biol Ther 5: 225-227.
86. Maldonado JL, Fridlyand J, Patel H, Jain AN, Busam K, Kageshita T, et al (2003) Determinants of BRAF mutations in primary melanomas. J Natl Cancer Inst 95: 1878-1890.
87. Markby DW, Onrust R, Bourne HR, (1993) Separate GTP binding and GTPase activating domains of a G alpha subunit. Science 262: 1895-1901.
88. Martin M, Masshofer L, Temming P, Rahmann S, Metz C, Bornfeld N, et al (2013) Exome sequencing identifies recurrent somatic mutations in EIF1AX and SF3B1 in uveal melanoma with disomy 3. Nat Genet 45: 933-936.
89. Michael BD, Syndikus I, Clark A, Baborie A, (2010) Diffuse primary leptomeningeal melanocytosis in a patient receiving a novel cancer cell vaccine for prostate cancer. BMJ Case Rep doi: 10.1136/bcr.11.2009.2495.
90. Miro J, Velasco R, Majos C, Gil M, Boluda S, Bruna J, (2011) Meningeal melanocytosis: a possibly useful treatment for a rare primary brain neoplasm. J Neurol 258: 1169-1171.
91. Mitsiades N, Chew SA, He B, Riechardt AI, Karadedou T, Kotoula V, Poulaki V, (2011) Genotype-dependent sensitivity of uveal melanoma cell lines to inhibition of B-Raf, MEK, and Akt kinases: rationale for personalized therapy. Invest Ophthalmol Vis Sci 52: 7248-7255.
92. Mooi WJKT, (2007a) Cutaneous nevi and other pigmented skin lesions. In: Pathology of Melanocytic Disorders., P Shaw, (ed.), p. 52. Hodder Arnold: London.
93. Mooi WJKT, (2007b) Melanin, melanocytes, skin. In: Pathology of Melanocytic Disorders., P Shaw, (ed.), p. 4. Hodder Arnold: London.
94. Mooi WJKT, (2007c) Melanin, melanocytes, skin. In: Pathology of Melanocytic Disorders., P Shaw, (ed.), p. 6. Hodder Arnold: London.
95. Munoz-Hidalgo L, Lopez-Gines C, Navarro L, Callaghan RC, San Miguel T, Gil-Benso R, et al (2014) BRAF V600E mutation in two distinct meningeal melanocytomas associated with a nevus of Ota. J Clin Oncol 32: 72-75.
96. Murali R, Wiesner T, Rosenblum MK, Bastian BC, (2012) GNAQ and GNA11 mutations in melanocytomas of the central nervous system. Acta Neuropathol 123: 457-459.
97. Muthappan M, Muthu T, Hussain Z, Lamont D, Balakrishnan V, (2012) Cervical intramedullary melanocytoma: a case report and review of literature. J Clin Neurosci 19: 1450-1453.
98. Nagashima Y, Miyagi Y, Aoki I, Funabiki T, Ikuta K, Umeda M, et al (1994) Establishment and characterization of a malignant melanoma cell line (YP-MEL) derived from a patient with neurocutaneous melanosis. Pathol Res Pract 190: 178-185.
99. Neer EJ, (1995) Heterotrimeric G proteins: organizers of transmembrane signals. Cell 80: 249-257.
100. Nikola Z, Dragan M, Mijovic Z, Milentijevic MJ, (2012) Primary leptomeningeal melanocytosis - a case report with an autopsy diagnosis. Vojnosanit Pregl 69: 631-634.
101. Niu HT, Zhou QM, Wang F, Shao Q, Guan YX, Wen XZ, et al (2013) Identification of anaplastic lymphoma kinase break points and oncogenic mutation profiles in acral/mucosal melanomas. Pigment Cell Melanoma Res 26: 646-653.
102. Onken MD, Worley LA, Long MD, Duan S, Council ML, Bowcock AM, Harbour JW, (2008) Oncogenic mutations in GNAQ occur early in uveal melanoma. Invest Ophthalmol Vis Sci 49: 5230-5234.
103. Pedersen M, Kusters-Vandevelde HV, Viros A, Groenen PJ, Sanchez-Laorden B, Gilhuis JH, et al (2013) Primary melanoma of the CNS in children is driven by congenital expression of oncogenic NRAS in melanocytes. Cancer Discov 3: 458-469.
104. Phadke PA, Rakheja D, Le LP, Selim MA, Kapur P, Davis A, et al (2011) Proliferative nodules arising within congenital melanocytic nevi: a histologic, immunohistochemical, and molecular analyses of 43 cases. Am J Surg Pathol 35: 656-669.
105. Pirini MG, Mascalchi M, Salvi F, Tassinari CA, Zanella L, Bacchini P, et al (2003) Primary diffuse meningeal melanomatosis: radiologic-pathologic correlation. AJNR Am J Neuroradiol 24: 115-118.
106. Posch C, Ortiz-Urda S, (2013) NRAS mutant melanoma-undrugable? Oncotarget 4: 494-495.
107. Puntervoll HE, Molven A, Akslen LA, (2014) Frequencies of KIT and GNAQ mutations in acral melanoma. J Cutan Pathol 41: 893-894.
108. Rades D, Heidenreich F, Tatagiba M, Brandis A, Karstens JH, (2001) Therapeutic options for meningeal melanocytoma. Case report. J Neurosurg Spine 95: 225-231.
109. Rebecca VW, Alicea GM, Paraiso KH, Lawrence H, Gibney GT, Smalley KS, (2014) Vertical inhibition of the MAPK pathway enhances therapeutic responses in NRAS-mutant melanoma. Pigment Cell Melanoma Res 27: 1154-1158.
110. Rivers JK, Bhayana S, Martinka M, (2001) Dural melanoma associated with ocular melanosis and multiple blue nevi. J Cutan Med Surg 5: 381-385.
111. Roberts PJ, Usary JE, Darr DB, Dillon PM, Pfefferle AD, Whittle MC, et al (2012) Combined PI3K/mTOR and MEK inhibition provides broad antitumor activity in faithful murine cancer models. Clin Cancer Res 18: 5290-5303.
112. Rodriguez FJ, Stratakis CA, Evans DG, (2012) Genetic predisposition to peripheral nerve neoplasia: diagnostic criteria and pathogenesis of neurofibromatoses, Carney complex, and related syndromes. Acta Neuropathol 123: 349-367.
113. Rodriguez y Baena R, Gaetani P, Danova M, Bosi F, Zappoli F, (1992) Primary solitary intracranial melanoma: case report and review of the literature. Surg Neurol 38: 26-37.
114. Ross EM, Wilkie TM, (2000) GTPase-activating proteins for heterotrimeric G proteins: regulators of G protein signaling (RGS) and RGS-like proteins. Annu Rev Biochem 69: 795-827.
115. Rothenbuhler A, Stratakis CA, (2010) Clinical and molecular genetics of Carney complex. Best Pract Res Clin Endocrinol Metab 24: 389-399.
116. Ruan Y, Kovalchuk A, Jayanthan A, Lun X, Nagashima Y, Kovalchuk O, et al (2014) Druggable targets in pediatric neurocutaneous melanocytosis: molecular and drug sensitivity studies in xenograft and ex vivo tumor cell culture to identify agents for therapy. Neuro-Oncol doi: 10.1093/neuonc/nou310. [Epub 12 Nov 2014].
117. Salgado CM, Basu D, Nikiforova M, Bauer BS, Johnson D, Rundell V, et al (2014) BRAF mutations are also associated with neurocutaneous melanocytosis and large/giant congenital melanocytic nevi. Pediatr Dev Pathol [Epub 9 Dec 2014].
118. Salpea P, Stratakis CA, (2014) Carney complex and McCune Albright syndrome: an overview of clinical manifestations and human molecular genetics. Mol Cell Endocrinol 386: 85-91.
119. Scheithauer BW, Louis DN, Hunter S, Woodruff JM, Antonescu CR, (2007) Schwannoma. Chapter 9. In: WHO Classification of Tumours of the Central Nervous System., DN Louis, H Ohgaki, OD Wiestler, WK Cavenee, (eds), pp. 152-155. International Agency for Research on Cancer: Lyon.
120. Seidl M, Zolnhofer G, Gunser S, Ennker J, Schafer W, Tietze L, (2013) Psammomatous melanotic schwannoma as indicator of a Carney complex. Pathologe 34: 343-346.
121. Shih F, Yip S, McDonald PJ, Chudley AE, Del Bigio MR, (2014) Oncogenic codon 13 NRAS mutation in a primary mesenchymal brain neoplasm and nevus of a child with neurocutaneous melanosis. Acta Neuropathol Commun 2: 140.
122. Shoushtari AN, Carvajal RD, (2014) GNAQ and GNA11 mutations in uveal melanoma. Melanoma Res 24: 525-534.
123. Skarli SO, Wolf AL, Kristt DA, Numaguchi Y, (1994) Melanoma arising in a cervical spinal nerve root: report of a case with a benign course and malignant features. Neurosurgery 34: 533-537.
124. Smith AB, Rushing EJ, Smirniotopoulos JG, (2009) Pigmented lesions of the central nervous system: radiologic-pathologic correlation. Radiographics 29: 1503-1524.
125. Soparker CN, O'Brien JM, Albert DM, (1993) Investigation of the role of the ras protooncogene point mutation in human uveal melanomas. Invest Ophthalmol Vis Sci 34: 2203-2209.
126. Strom RG, Shvartsbeyn M, Rosenblum MK, Hameed MR, Nafa K, Mikolaenko I, Babu RP, (2012) Melanocytic tumor with GNA11 p.Q209L mutation mimicking a foramen magnum meningioma. Clin Neurol Neurosurg 114: 1197-1200.
127. Subbiah V, Wolff JE, (2010) Rapid response to therapy of neurocutaneous melanosis with leptomeningeal melanoma. Pediatr Blood Cancer 54: 180-181.
128. Takayama H, La Rochelle WJ, Anver M, Bockman DE, Merlino G, (1996) Scatter factor/hepatocyte growth factor as a regulator of skeletal muscle and neural crest development. Proc Natl Acad Sci U S A 93: 5866-5871.
129. Tolleson WH, (2005) Human melanocyte biology, toxicology, and pathology. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 23: 105-161.
130. Torres-Mora J, Dry S, Li X, Binder S, Amin M, Folpe AL, (2014) Malignant melanotic schwannian tumor: a clinicopathologic, immunohistochemical, and gene expression profiling study of 40 cases, with a proposal for the reclassification of "melanotic schwannoma". Am J Surg Pathol 38: 94-105.
131. Tripathy K, Misra A, Misra D, Pujari S, Nayak M, Rath J, (2011) Melanotic choroid plexus carcinoma of the posterior fossa. J Clin Neurol 7: 105-106.
132. Uozumi Y, Kawano T, Kawaguchi T, Kaneko Y, Ooasa T, Ogasawara S, et al (2003) Malignant transformation of meningeal melanocytoma: a case report. Brain Tumor Pathol 20: 21-25.
133. Van Raamsdonk CD, Bezrookove V, Green G, Bauer J, Gaugler L, O'Brien JM, et al (2009) Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi. Nature 457: 599-602.
134. Van Raamsdonk CD, Griewank KG, Crosby MB, Garrido MC, Vemula S, Wiesner T, et al (2010) Mutations in GNA11 in uveal melanoma. N Engl J Med 363: 2191-2199.
135. Virchow R, (1859) Pigment und diffuse Melanose der Arachnoides. Virchows Arch 16: 180-182.
136. de Vries E, Coebergh JW, (2005) Melanoma incidence has risen in Europe. BMJ 331: 698.
137. Wallander ML, Layfield LJ, Emerson LL, Mamalis N, Davis D, Tripp SR, Holden JA, (2011) KIT mutations in ocular melanoma: frequency and anatomic distribution. Mod Pathol 24: 1031-1035.
138. Wang F, Li X, Chen L, Pu X, (2007) Malignant transformation of spinal meningeal melanocytoma. Case report and review of the literature. J Neurosurg Spine 6: 451-454.
139. Wang H, Zhang S, Wu C, Zhang Z, Qin T, (2013) Melanocytomas of the central nervous system: a clinicopathological and molecular study. Eur J Clin Invest 43: 809-815.
140. Weber A, Hengge UR, Urbanik D, Markwart A, Mirmohammadsaegh A, Reichel MB, et al (2003) Absence of mutations of the BRAF gene and constitutive activation of extracellular-regulated kinase in malignant melanomas of the uvea. Lab Invest 83: 1771-1776.
141. Whiteman DC, Pavan WJ, Bastian BC, (2011) The melanomas: a synthesis of epidemiological, clinical, histopathological, genetic, and biological aspects, supporting distinct subtypes, causal pathways, and cells of origin. Pigment Cell Melanoma Res 24: 879-897.
142. Wilkie TM, Gilbert DJ, Olsen AS, Chen XN, Amatruda TT, Korenberg JR, et al (1992) Evolution of the mammalian G protein alpha subunit multigene family. Nat Genet 1: 85-91.
143. Wright CJ, McCormack PL, (2013) Trametinib: first global approval. Drugs 73: 1245-1254.
144. Wu X, Li J, Zhu M, Fletcher JA, Hodi FS, (2012) Protein kinase C inhibitor AEB071 targets ocular melanoma harboring GNAQ mutations via effects on the PKC/Erk1/2 and PKC/NF-kappaB pathways. Mol Cancer Ther 11: 1905-1914.
145. Wu X, Zhu M, Fletcher JA, Giobbie-Hurder A, Hodi FS, (2012) The protein kinase C inhibitor enzastaurin exhibits antitumor activity against uveal melanoma. PLoS ONE 7: e29622.
146. Yu FX, Luo J, Mo JS, Liu G, Kim YC, Meng Z, et al (2014) Mutant Gq/11 promote uveal melanoma tumorigenesis by activating YAP. Cancer Cell 25: 822-830.
147. Yu FX, Zhao B, Panupinthu N, Jewell JL, Lian I, Wang LH, et al (2012) Regulation of the Hippo-YAP pathway by G-protein-coupled receptor signaling. Cell 150: 780-791.
148. Zuidervaart W, van Nieuwpoort F, Stark M, Dijkman R, Packer L, Borgstein AM, et al (2005) Activation of the MAPK pathway is a common event in uveal melanomas although it rarely occurs through mutation of BRAF or RAS. Br J Cancer 92: 2032-2038.