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Understanding Melanoma Progression by Gene Expression Signatures

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Cancer Genomics

Abstract

Malignant melanoma is the most aggressive cancer in humans and understanding this unique biological behavior may help to design better prognosticators and more efficient therapies. However, malignant melanoma is a heterogenous tumor etiologically (UV-induced or not), morphologically and genetically driven by various oncogens (B-RAF, N-RAS, KIT) and suppressor genes (CDKN2A, p53, PTEN). There are a significant number of studies in which prognostic gene and protein signatures were defined based on either analysis of the primary tumors (metastasis initiating gene set) or melanoma metastases (metastasis maintenance gene set) affecting progression of the disease or survival of the patient. These studies provided prognostic signatures of minimal overlap. Here we demonstrate consensus prognostic gene and protein sets derived from primary and metastatic tumor tissues. It is of note that although there were rare overlaps concerning the composing individual genes in these sets, network analysis defined the common pathways driving melanoma progression: cell proliferation, apoptosis, motility, and immune mechanisms. Malignant melanoma is chemoresistant, the genetic background of which has been unknown for a long time, but new genomic analyses have identified complex genetic alterations responsible for this phenotype involving DNA repair genes and oncogene signaling pathways. The advent of immunotherapy of melanoma placed the previously defined immune signature-associated genomic prognosticators into a new perspective, suggesting that it might also be a powerful predictor. Target therapy of malignant melanoma has changed the standard therapy based on IFN and dacarbazine. Target therapy of B-RAF and KIT mutated melanomas is based on careful selection of tumors with activating/sensitizing mutations, but has immediately raised the issue of genetic basis of constitutive or acquired resistances.

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References

  1. Balch CM, Soong S-J, Thompson JF (2004) The natural history of melanoma and factors predicting outcome. In: Thompson JF, Morton DL, Kroon BBR (eds) Textbook of melanoma. Taylor & Francis Group, London/New York, pp 181–199

    Google Scholar 

  2. Vidwans SJ, Flaherty KT, Fisher DE, Tenenbaum JM, Travers MD, Shrager J (2011) A melanoma molecular disease model. PLoS One 6(3):e18257. doi: 10.1371/journal.pone.0018257

    Article  CAS  PubMed  Google Scholar 

  3. Viros A, Fridlyand J, Bauer J, Lasithiotakis K, Garbe C, Pinkel D, Bastian BC (2008) Improving melanoma classification by integrating genetic and morphologic features. PLoS Med 5(6):e120. doi: 07-PLME-RA-2081[pii]10.1371/journal.pmed.0050120

    Article  PubMed  Google Scholar 

  4. Takata M, Murata H, Saida T (2009) Molecular pathogenesis of malignant melanoma: a different perspective from the studies of melanocytic nevus and acral melanoma. Pigment Cell Melanoma Res 23(1):64–71. doi: PCR645[pii]10.1111/j.1755-148X.2009.00645.x

    Article  PubMed  Google Scholar 

  5. 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(5):879–897. doi: 10.1111/j.1755-148X.2011.00880.x

    Article  CAS  PubMed  Google Scholar 

  6. Wei X, Walia V, Lin JC, Teer JK, Prickett TD, Gartner J, Davis S, Stemke-Hale K, Davies MA, Gershenwald JE, Robinson W, Robinson S, Rosenberg SA, Samuels Y (2011) Exome sequencing identifies GRIN2A as frequently mutated in melanoma. Nat Genet 43(5):442–446. doi: ng.810[pii]10.1038/ng.810

    Article  CAS  PubMed  Google Scholar 

  7. Haq R, Fisher DE (2011) Biology and clinical relevance of the micropthalmia family of transcription factors in human cancer. J Clin Oncol 29(25):3474–3482. doi: JCO.2010.32.6223[pii]10.1200/JCO.2010.32.6223

    Article  CAS  PubMed  Google Scholar 

  8. Mustika R, Budiyanto A, Nishigori C, Ichihashi M, Ueda M (2005) Decreased expression of Apaf-1 with progression of melanoma. Pigment Cell Res 18(1):59–62. doi: PCR205[pii]10.1111/j.1600-0749.2004.00205.x

    Article  CAS  PubMed  Google Scholar 

  9. Deli T, Varga N, Adam A, Kenessey I, Raso E, Puskas LG, Tovari J, Fodor J, Feher M, Szigeti GP, Csernoch L, Timar J (2007) Functional genomics of calcium channels in human melanoma cells. Int J Cancer 121(1):55–65. doi: 10.1002/ijc.22621

    Article  CAS  PubMed  Google Scholar 

  10. Gyorffy B, Lage H (2007) A web-based data warehouse on gene expression in human malignant melanoma. J Invest Dermatol 127(2):394–399. doi: 5700543[pii]10.1038/sj.jid.5700543

    Article  PubMed  Google Scholar 

  11. Cochran AJ, Bailly C, Paul E, Remotti F, Bhuta S (1997) Characteristics that relate to prognosis. In: Melanocytic tumors. Lippincott-Raven Publishers, Philadelphia

    Google Scholar 

  12. Manola J, Atkins M, Ibrahim J, Kirkwood J (2000) Prognostic factors in metastatic melanoma: a pooled analysis of Eastern Cooperative Oncology Group trials. J Clin Oncol 18(22):3782–3793

    CAS  PubMed  Google Scholar 

  13. Streit M, Detmar M (2003) Angiogenesis, lymphangiogenesis, and melanoma metastasis. Oncogene 22(20):3172–3179. doi: 10.1038/sj.onc.12064571206457[pii]

    Article  CAS  PubMed  Google Scholar 

  14. Dome B, Hendrix MJ, Paku S, Tovari J, Timar J (2007) Alternative vascularization mechanisms in cancer: pathology and therapeutic implications. Am J Pathol 170(1):1–15. doi: S-9440(10)60829-2[pii]10.2353/ajpath.2007.060302

    Article  CAS  PubMed  Google Scholar 

  15. Ladanyi A, Somlai B, Gilde K, Fejos Z, Gaudi I, Timar J (2004) T-cell activation marker expression on tumor-infiltrating lymphocytes as prognostic factor in cutaneous malignant melanoma. Clin Cancer Res 10(2):521–530

    Article  CAS  PubMed  Google Scholar 

  16. Ladanyi A, Kiss J, Somlai B, Gilde K, Fejos Z, Mohos A, Gaudi I, Timar J (2007) Density of DC-LAMP(+) mature dendritic cells in combination with activated T lymphocytes infiltrating primary cutaneous melanoma is a strong independent prognostic factor. Cancer Immunol Immunother 56(9):1459–1469. doi: 10.1007/s00262-007-0286-3

    Article  PubMed  Google Scholar 

  17. Jacobs JF, Nierkens S, Figdor CG, de Vries IJ, Adema GJ (2012) Regulatory T cells in melanoma: the final hurdle towards effective immunotherapy? Lancet Oncol 13(1):e32–e42. doi: S1470-2045(11)70155-3[pii]10.1016/S1470-2045(11)70155-3

    Article  CAS  PubMed  Google Scholar 

  18. Ladanyi A, Timar J, Bocsi J, Tovari J, Lapis K (1995) Sex-dependent liver metastasis of human melanoma lines in SCID mice. Melanoma Res 5(2):83–86

    Article  CAS  PubMed  Google Scholar 

  19. Seiter S, Schadendorf D, Herrmann K, Schneider M, Rosel M, Arch R, Tilgen W, Zoller M (1996) Expression of CD44 variant isoforms in malignant melanoma. Clin Cancer Res 2(3):447–456

    CAS  PubMed  Google Scholar 

  20. Dome B, Somlai B, Ladanyi A, Fazekas K, Zoller M, Timar J (2001) Expression of CD44v3 splice variant is associated with the visceral metastatic phenotype of human melanoma. Virchows Arch 439(5):628–635

    CAS  PubMed  Google Scholar 

  21. Girouard SD, Murphy GF (2011) Melanoma stem cells: not rare, but well done. Lab Invest 91(5):647–664. doi: labinvest201150[pii]10.1038/labinvest.2011.50

    Article  PubMed  Google Scholar 

  22. Dome B, Somlai B, Timar J (2000) The loss of NM23 protein in malignant melanoma predicts lymphatic spread without affecting survival. Anticancer Res 20(5C):3971–3974

    CAS  PubMed  Google Scholar 

  23. Lee JH, Miele ME, Hicks DJ, Phillips KK, Trent JM, Weissman BE, Welch DR (1996) KiSS-1, a novel human malignant melanoma metastasis-suppressor gene. J Natl Cancer Inst 88(23):1731–1737

    Article  CAS  PubMed  Google Scholar 

  24. Albelda SM, Mette SA, Elder DE, Stewart R, Damjanovich L, Herlyn M, Buck CA (1990) Integrin distribution in malignant melanoma: association of the beta 3 subunit with tumor progression. Cancer Res 50(20):6757–6764

    CAS  PubMed  Google Scholar 

  25. Dai DL, Makretsov N, Campos EI, Huang C, Zhou Y, Huntsman D, Martinka M, Li G (2003) Increased expression of integrin-linked kinase is correlated with melanoma progression and poor patient survival. Clin Cancer Res 9(12):4409–4414

    CAS  PubMed  Google Scholar 

  26. Kim M, Gans JD, Nogueira C, Wang A, Paik JH, Feng B, Brennan C, Hahn WC, Cordon-Cardo C, Wagner SN, Flotte TJ, Duncan LM, Granter SR, Chin L (2006) Comparative oncogenomics identifies NEDD9 as a melanoma metastasis gene. Cell 125(7):1269–1281. doi: S0092-8674(06)00718-5[pii]10.1016/j.cell.2006.06.008

    Article  CAS  PubMed  Google Scholar 

  27. Natali PG, Nicotra MR, Di Renzo MF, Prat M, Bigotti A, Cavaliere R, Comoglio PM (1993) Expression of the c-Met/HGF receptor in human melanocytic neoplasms: demonstration of the relationship to malignant melanoma tumour progression. Br J Cancer 68(4):746–750

    Article  CAS  PubMed  Google Scholar 

  28. Timar J, Raso E, Dome B, Ladanyi A, Banfalvi T, Gilde K, Raz A (2002) Expression and function of the AMF receptor by human melanoma in experimental and clinical systems. Clin Exp Metastasis 19(3):225–232

    Article  CAS  PubMed  Google Scholar 

  29. Strizzi L, Hardy KM, Kirsammer GT, Gerami P, Hendrix MJ (2011) Embryonic signaling in melanoma: potential for diagnosis and therapy. Lab Invest 91(6):819–824. doi: labinvest201163[pii]10.1038/labinvest.2011.63

    Article  CAS  PubMed  Google Scholar 

  30. Timar J, Tovari J, Raso E, Meszaros L, Bereczky B, Lapis K (2005) Platelet-mimicry of cancer cells: epiphenomenon with clinical significance. Oncology 69(3):185–201. doi: 88069[pii]10.1159/000088069

    Article  PubMed  Google Scholar 

  31. Braeuer RR, Zigler M, Villares GJ, Dobroff AS, Bar-Eli M (2011) Transcriptional control of melanoma metastasis: the importance of the tumor microenvironment. Semin Cancer Biol 21(2):83–88. doi: S1044-579X(10)00126-4[pii]10.1016/j.semcancer.2010.12.007

    Article  CAS  PubMed  Google Scholar 

  32. Bittner M, Meltzer P, Chen Y, Jiang Y, Seftor E, Hendrix M, Radmacher M, Simon R, Yakhini Z, Ben-Dor A, Sampas N, Dougherty E, Wang E, Marincola F, Gooden C, Lueders J, Glatfelter A, Pollock P, Carpten J, Gillanders E, Leja D, Dietrich K, Beaudry C, Berens M, Alberts D, Sondak V (2000) Molecular classification of cutaneous malignant melanoma by gene expression profiling. Nature 406(6795):536–540. doi: 10.1038/35020115

    Article  CAS  PubMed  Google Scholar 

  33. Mandruzzato S, Callegaro A, Turcatel G, Francescato S, Montesco MC, Chiarion-Sileni V, Mocellin S, Rossi CR, Bicciato S, Wang E, Marincola FM, Zanovello P (2006) A gene expression signature associated with survival in metastatic melanoma. J Transl Med 4:50. doi: 1479-5876-4-50[pii]10.1186/1479-5876-4-50

    Article  PubMed  Google Scholar 

  34. Winnepenninckx V, Lazar V, Michiels S, Dessen P, Stas M, Alonso SR, Avril MF, Ortiz Romero PL, Robert T, Balacescu O, Eggermont AM, Lenoir G, Sarasin A, Tursz T, van den Oord JJ, Spatz A (2006) Gene expression profiling of primary cutaneous melanoma and clinical outcome. J Natl Cancer Inst 98(7):472–482. doi: 98/7/472[pii]10.1093/jnci/djj103

    Article  CAS  PubMed  Google Scholar 

  35. John T, Black MA, Toro TT, Leader D, Gedye CA, Davis ID, Guilford PJ, Cebon JS (2008) Predicting clinical outcome through molecular profiling in stage III melanoma. Clin Cancer Res 14(16):5173–5180. doi: 14/16/5173[pii]10.1158/1078-0432.CCR-07-4170

    Article  CAS  PubMed  Google Scholar 

  36. Conway C, Mitra A, Jewell R, Randerson-Moor J, Lobo S, Nsengimana J, Edward S, Sanders DS, Cook M, Powell B, Boon A, Elliott F, de Kort F, Knowles MA, Bishop DT, Newton-Bishop J (2009) Gene expression profiling of paraffin-embedded primary melanoma using the DASL assay identifies increased osteopontin expression as predictive of reduced relapse-free survival. Clin Cancer Res 15(22):6939–6946. doi: 1078-0432.CCR-09-1631[pii]10.1158/1078-0432.CCR-09-1631

    Article  CAS  PubMed  Google Scholar 

  37. Bogunovic D, O’Neill DW, Belitskaya-Levy I, Vacic V, Yu YL, Adams S, Darvishian F, Berman R, Shapiro R, Pavlick AC, Lonardi S, Zavadil J, Osman I, Bhardwaj N (2009) Immune profile and mitotic index of metastatic melanoma lesions enhance clinical staging in predicting patient survival. Proc Natl Acad Sci USA 106(48):20429–20434. doi: 0905139106[pii]10.1073/pnas.0905139106

    Article  CAS  PubMed  Google Scholar 

  38. Jonsson G, Busch C, Knappskog S, Geisler J, Miletic H, Ringner M, Lillehaug JR, Borg A, Lonning PE (2010) Gene expression profiling-based identification of molecular subtypes in stage IV melanomas with different clinical outcome. Clin Cancer Res 16(13):3356–3367. doi: 1078-0432.CCR-09-2509[pii]10.1158/1078-0432.CCR-09-2509

    Article  PubMed  Google Scholar 

  39. Scott KL, Nogueira C, Heffernan TP, van Doorn R, Dhakal S, Hanna JA, Min C, Jaskelioff M, **ao Y, Wu CJ, Cameron LA, Perry SR, Zeid R, Feinberg T, Kim M, Vande Woude G, Granter SR, Bosenberg M, Chu GC, DePinho RA, Rimm DL, Chin L (2011) Proinvasion metastasis drivers in early-stage melanoma are oncogenes. Cancer Cell 20(1):92–103. doi: S1535-6108(11)00195-4[pii]10.1016/j.ccr.2011.05.025

    Article  CAS  PubMed  Google Scholar 

  40. Lugassy C, Lazar V, Dessen P, van den Oord JJ, Winnepenninckx V, Spatz A, Bagot M, Bensussan A, Janin A, Eggermont AM, Barnhill RL (2011) Gene expression profiling of human angiotropic primary melanoma: selection of 15 differentially expressed genes potentially involved in extravascular migratory metastasis. Eur J Cancer 47(8):1267–1275. doi: S0959-8049(11)00033-5[pii]10.1016/j.ejca.2011.01.009

    Article  CAS  PubMed  Google Scholar 

  41. Schramm SJ, Mann GJ (2011) Melanoma prognosis: a REMARK-based systematic review and bioinformatic analysis of immunohistochemical and gene microarray studies. Mol Cancer Ther 10(8):1520–1528. doi: 1535-7163.MCT-10-0901[pii]10.1158/1535-7163.MCT-10-0901

    Article  CAS  PubMed  Google Scholar 

  42. Gould Rothberg BE, Berger AJ, Molinaro AM, Subtil A, Krauthammer MO, Camp RL, Bradley WR, Ariyan S, Kluger HM, Rimm DL (2009) Melanoma prognostic model using tissue microarrays and genetic algorithms. J Clin Oncol 27(34):5772–5780. doi: JCO.2009.22.8239[pii]10.1200/JCO.2009.22.8239

    Article  PubMed  Google Scholar 

  43. Gould Rothberg BE, Bracken MB, Rimm DL (2009) Tissue biomarkers for prognosis in cutaneous melanoma: a systematic review and meta-analysis. J Natl Cancer Inst 101(7):452–474. doi: djp038[pii]10.1093/jnci/djp038

    Article  PubMed  Google Scholar 

  44. Schramm SJ, Campain AE, Scolyer RA, Yang YH, Mann GJ (2012) Review and cross-validation of gene expression signatures and melanoma prognosis. J Invest Dermatol 132(2):274–283. doi: jid2011305[pii]10.1038/jid.2011.305

    Article  CAS  PubMed  Google Scholar 

  45. Becker B, Roesch A, Hafner C, Stolz W, Dugas M, Landthaler M, Vogt T (2004) Discrimination of melanocytic tumors by cDNA array hybridization of tissues prepared by laser pressure catapulting. J Invest Dermatol 122(2):361–368. doi: 22240[pii]10.1046/j.0022-202X.2004.22240.x

    Article  CAS  PubMed  Google Scholar 

  46. Haqq C, Nosrati M, Sudilovsky D, Crothers J, Khodabakhsh D, Pulliam BL, Federman S, Miller JR 3rd, Allen RE, Singer MI, Leong SP, Ljung BM, Sagebiel RW, Kashani-Sabet M (2005) The gene expression signatures of melanoma progression. Proc Natl Acad Sci USA 102(17):6092–6097. doi: 0501564102[pii]10.1073/pnas.0501564102

    Article  CAS  PubMed  Google Scholar 

  47. Jaeger J, Koczan D, Thiesen HJ, Ibrahim SM, Gross G, Spang R, Kunz M (2007) Gene expression signatures for tumor progression, tumor subtype, and tumor thickness in laser-microdissected melanoma tissues. Clin Cancer Res 13(3):806–815. doi: 13/3/806[pii]10.1158/1078-0432.CCR-06-1820

    Article  CAS  PubMed  Google Scholar 

  48. Riker AI, Enkemann SA, Fodstad O, Liu S, Ren S, Morris C, ** Y, Howell P, Metge B, Samant RS, Shevde LA, Li W, Eschrich S, Daud A, Ju J, Matta J (2008) The gene expression profiles of primary and metastatic melanoma yields a transition point of tumor progression and metastasis. BMC Med Genomics 1:13. doi: 1755-8794-1-13[pii]10.1186/1755-8794-1-13

    Article  PubMed  Google Scholar 

  49. Jewell R, Mitra A, Conway C, Iremonger J, Walker C, de Kort F, Cook M, Boon A, Speirs V, Newton-Bishop J (2011) Identification of differentially expressed genes in matched formalin-fixed paraffin-embedded primary and metastatic melanoma tumor pairs. Pigment Cell Melanoma Res. doi: 10.1111/j.1755-148X.2011.00965.x

    Google Scholar 

  50. Timar J, Gyorffy B, Raso E (2010) Gene signature of the metastatic potential of cutaneous melanoma: too much for too little? Clin Exp Metastasis 27(6):371–387. doi: 10.1007/s10585-010-9307-2

    Article  CAS  PubMed  Google Scholar 

  51. Gould Rothberg BE, Rimm DL (2011) Biomarkers: the useful and the not so useful–an assessment of molecular prognostic markers for cutaneous melanoma. J Invest Dermatol 130(8):1971–1987. doi: jid2010149[pii]10.1038/jid.2010.149

    Article  Google Scholar 

  52. Tawbi HA, Villaruz L, Tarhini A, Moschos S, Sulecki M, Viverette F, Shipe-Spotloe J, Radkowski R, Kirkwood JM (2011) Inhibition of DNA repair with MGMT pseudosubstrates: phase I study of lomeguatrib in combination with dacarbazine in patients with advanced melanoma and other solid tumours. Br J Cancer 105(6):773–777. doi: bjc2011285[pii]10.1038/bjc.2011.285

    Article  CAS  PubMed  Google Scholar 

  53. Busch C, Geisler J, Lillehaug JR, Lonning PE (2010) MGMT expression levels predict disease stabilisation, progression-free and overall survival in patients with advanced melanomas treated with DTIC. Eur J Cancer 46(11):2127–2133. doi: S0959-8049(10)00364-3[pii]10.1016/j.ejca.2010.04.023

    Article  PubMed  Google Scholar 

  54. Gallagher SJ, Thompson JF, Indsto J, Scurr LL, Lett M, Gao BF, Dunleavey R, Mann GJ, Kefford RF, Rizos H (2008) p16INK4a expression and absence of activated B-RAF are independent predictors of chemosensitivity in melanoma tumors. Neoplasia 10(11):1231–1239

    CAS  PubMed  Google Scholar 

  55. Jewell R, Conway C, Mitra A, Randerson-Moor J, Lobo S, Nsengimana J, Harland M, Marples M, Edward S, Cook M, Powell B, Boon A, de Kort F, Parker KA, Cree IA, Barrett JH, Knowles MA, Bishop DT, Newton-Bishop J (2010) Patterns of expression of DNA repair genes and relapse from melanoma. Clin Cancer Res 16(21):5211–5221. doi: 1078-0432.CCR-10-1521[pii]10.1158/1078-0432.CCR-10-1521

    Article  CAS  PubMed  Google Scholar 

  56. Ascierto PA, Kirkwood JM (2008) Adjuvant therapy of melanoma with interferon: lessons of the past decade. J Transl Med 6:62. doi: 1479-5876-6-62[pii]10.1186/1479-5876-6-62

    Article  PubMed  Google Scholar 

  57. Timar J, Meszaros L, Ladanyi A, Puskas LG, Raso E (2006) Melanoma genomics reveals signatures of sensitivity to bio- and targeted therapies. Cell Immunol 244(2):154–157. doi: S0008-8749(07)00061-5[pii]10.1016/j.cellimm.2006.12.009

    Article  CAS  PubMed  Google Scholar 

  58. Krepler C, Certa U, Wacheck V, Jansen B, Wolff K, Pehamberger H (2004) Pegylated and conventional interferon-alpha induce comparable transcriptional responses and inhibition of tumor growth in a human melanoma SCID mouse xenotransplantation model. J Invest Dermatol 123(4):664–669. doi: 10.1111/j.0022-202X.2004.23433.xJID23433[pii]

    Article  CAS  PubMed  Google Scholar 

  59. Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbe C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363(8):711–723. doi: NEJMoa1003466[pii]10.1056/NEJMoa1003466

    Article  CAS  PubMed  Google Scholar 

  60. Robert C, Thomas L, Bondarenko I, O’Day S, Weber J, Garbe C, Lebbe C, Baurain JF, Testori A, Grob JJ, Davidson N, Richards J, Maio M, Hauschild A, Miller WH Jr, Gascon P, Lotem M, Harmankaya K, Ibrahim R, Francis S, Chen TT, Humphrey R, Hoos A, Wolchok JD (2011) Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med 364(26):2517–2526. doi: 10.1056/NEJMoa1104621

    Article  CAS  PubMed  Google Scholar 

  61. Flaherty KT, Puzanov I, Kim KB, Ribas A, McArthur GA, Sosman JA, O’Dwyer PJ, Lee RJ, Grippo JF, Nolop K, Chapman PB (2010) Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med 363(9):809–819. doi: 10.1056/NEJMoa1002011

    Article  CAS  PubMed  Google Scholar 

  62. Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, Dummer R, Garbe C, Testori A, Maio M, Hogg D, Lorigan P, Lebbe C, Jouary T, Schadendorf D, Ribas A, O’Day SJ, Sosman JA, Kirkwood JM, Eggermont AM, Dreno B, Nolop K, Li J, Nelson B, Hou J, Lee RJ, Flaherty KT, McArthur GA (2011) Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 364(26):2507–2516. doi: 10.1056/NEJMoa1103782

    Article  CAS  PubMed  Google Scholar 

  63. Nazarian R, Shi H, Wang Q, Kong X, Koya RC, Lee H, Chen Z, Lee MK, Attar N, Sazegar H, Chodon T, Nelson SF, McArthur G, Sosman JA, Ribas A, Lo RS (2010) Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation. Nature 468(7326):973–977. doi: nature09626[pii]10.1038/nature09626

    Article  CAS  PubMed  Google Scholar 

  64. Wagle N, Emery C, Berger MF, Davis MJ, Sawyer A, Pochanard P, Kehoe SM, Johannessen CM, Macconaill LE, Hahn WC, Meyerson M, Garraway LA (2011) Dissecting therapeutic resistance to RAF inhibition in melanoma by tumor genomic profiling. J Clin Oncol 29(22):3085–3096. doi: JCO.2010.33.2312[pii]10.1200/JCO.2010.33.2312

    Article  CAS  PubMed  Google Scholar 

  65. Johannessen CM, Boehm JS, Kim SY, Thomas SR, Wardwell L, Johnson LA, Emery CM, Stransky N, Cogdill AP, Barretina J, Caponigro G, Hieronymus H, Murray RR, Salehi-Ashtiani K, Hill DE, Vidal M, Zhao JJ, Yang X, Alkan O, Kim S, Harris JL, Wilson CJ, Myer VE, Finan PM, Root DE, Roberts TM, Golub T, Flaherty KT, Dummer R, Weber BL, Sellers WR, Schlegel R, Wargo JA, Hahn WC, Garraway LA (2010) COT drives resistance to RAF inhibition through MAP kinase pathway reactivation. Nature 468(7326):968–972. doi: nature09627[pii]10.1038/nature09627

    Article  CAS  PubMed  Google Scholar 

  66. Guo J, Si L, Kong Y, Flaherty KT, Xu X, Zhu Y, Corless CL, Li L, Li H, Sheng X, Cui C, Chi Z, Li S, Han M, Mao L, Lin X, Du N, Zhang X, Li J, Wang B, Qin S (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(21):2904–2909. doi: JCO.2010.33.9275[pii]10.1200/JCO.2010.33.9275

    Article  CAS  PubMed  Google Scholar 

  67. Carvajal RD, Antonescu CR, Wolchok JD, Chapman PB, Roman RA, Teitcher J, Panageas KS, Busam KJ, Chmielowski B, Lutzky J, Pavlick AC, Fusco A, Cane L, Takebe N, Vemula S, Bouvier N, Bastian BC, Schwartz GK (2011) KIT as a therapeutic target in metastatic melanoma. JAMA 305(22):2327–2334. doi: 305/22/2327[pii]10.1001/jama.2011.746

    Article  CAS  PubMed  Google Scholar 

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Acknowledgement

This work was supported by grants ETT and TAMOP 4.2.1B.-09/1/KMR-2010-0001.

Author information

Authors and Affiliations

  1. 2nd Department of Pathology, Semmelweis University, Budapest, Hungary

    J. Tímár, T. Barbai, B. Győrffy & E. Rásó

  2. Tumor Progression Research Group, National Academy of Sciences-Semmelweis University, Budapest, Hungary

    J. Tímár & E. Rásó

Authors
  1. J. Tímár
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  2. T. Barbai
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  3. B. Győrffy
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  4. E. Rásó
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Correspondence to J. Tímár .

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Editors and Affiliations

  1. , Integrated Molecular Pathology, National Cancer Research Institute, Largo Rosanna Benzi 10, Genova, 16132, Italy

    Ulrich Pfeffer

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© 2013 Springer Science+Business Media Dordrecht

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Tímár, J., Barbai, T., Győrffy, B., Rásó, E. (2013). Understanding Melanoma Progression by Gene Expression Signatures. In: Pfeffer, U. (eds) Cancer Genomics. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5842-1_2

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