Skip to main content
SpringerLink
Log in

Gene Expression Profiling in Melanoma

  • Chapter
  • First Online:
Skin Cancer

Part of the book series: Current Clinical Pathology ((CCPATH))

  • 5184 Accesses

Abstract

One of the big challenges in cancer research is to identify genomic alterations responsible for genesis and progression of disease. Melanoma is one of the most difficult tumours to treat for its aggressiveness, strong therapeutic resistance and proclivity for late metastasis. Here we describe the new gene high-throughput technologies, microarray and next-generation sequencing (NGS), and their impact in melanoma research. We illustrate their use from the discovery of melanoma biomarkers and therapeutic targets to clinical applications including patients’ classification and stratification.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Tsao H, Atkins MB, Sober AJ. Management of cutaneous melanoma. N Engl J Med. 2004;351(10):998–1012.

    Article  PubMed  CAS  Google Scholar 

  2. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009;59(4):225–49.

    Article  PubMed  Google Scholar 

  3. Korn EL, Liu PY, Lee SJ, et al. Meta-analysis of phase II cooperative group trials in metastatic stage IV melanoma to determine progression-free and overall survival benchmarks for future phase II trials. J Clin Oncol. 2008;26(4):527–34.

    Article  PubMed  Google Scholar 

  4. Herlyn M, Ferrone S, Ronai Z, Finerty J, Pelroy R, Mohla S. Melanoma biology and progression. Cancer Res. 2001;61(11):4642–3.

    PubMed  CAS  Google Scholar 

  5. Van’t Veer LJ, Dai H, van de Vijver MJ, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002;415(6871):530–6.

    Article  Google Scholar 

  6. Venter JC, Adams MD, Myers EW, et al. The sequence of the human genome. Science. 2001;291(5507):1304–51.

    Article  PubMed  CAS  Google Scholar 

  7. West M, Ginsburg GS, Huang AT, Nevins JR. Embracing the complexity of genomic data for personalized medicine. Genome Res. 2006;16(5):559–66.

    Article  PubMed  CAS  Google Scholar 

  8. Schena M, Shalon D, Davis RW, Brown PO. Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science. 1995;270(5235):467–70.

    Article  PubMed  CAS  Google Scholar 

  9. Shalon D, Smith SJ, Brown PO. A DNA microarray system for analyzing complex DNA samples using two-color fluorescent probe hybridization. Genome Res. 1996;6(7):639–45.

    Article  PubMed  CAS  Google Scholar 

  10. Gunderson KL, Kruglyak S, Graige MS, et al. Decoding randomly ordered DNA arrays. Genome Res. 2004;14(5):870–7.

    Article  PubMed  CAS  Google Scholar 

  11. Sanges R, Cordero F, Calogero RA. oneChannelGUI: a graphical interface to Bioconductor tools, designed for life scientists who are not familiar with R language. Bioinformatics. 2007;23(24):3406–8.

    Article  PubMed  CAS  Google Scholar 

  12. Bolstad BM, Irizarry RA, Astrand M, Speed TP. A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics. 2003;19(2):185–93.

    Article  PubMed  CAS  Google Scholar 

  13. von Heydebreck A, Huber W, Gentleman RC. Differential expression of the Bioconductor Project. Bioconductor Project Working Papers. 2004;Working Paper 7.

    Google Scholar 

  14. Jeffery IB, Higgins DG, Culhane AC. Comparison and evaluation of methods for generating differentially expressed gene lists from microarray data. BMC Bioinformatics. 2006;7:359.

    Article  PubMed  Google Scholar 

  15. Subramanian A, Tamayo P, Mootha VK, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005;102(43):15545–50.

    Article  PubMed  CAS  Google Scholar 

  16. Ronaghi M. Pyrosequencing sheds light on DNA sequencing. Genome Res. 2001;11(1):3–11.

    Article  PubMed  CAS  Google Scholar 

  17. Hash Functions. Dr. Dobb’s Web site. http://drdobbs.com/database/184410284. Accessed 4 Sept 1997.

  18. Burrows M, Wheeler D. A block sorting lossless data compression algorithm. Technical Report 124, Digital Equipment Corporation. 1994.

    Google Scholar 

  19. Smith TF, Waterman MS. Identification of common molecular subsequences. J Mol Biol. 1981;147(1):195–7.

    Article  PubMed  CAS  Google Scholar 

  20. Sanger F, Coulson AR, Barrell BG, Smith AJ, Roe BA. Cloning in single-stranded bacteriophage as an aid to rapid DNA sequencing. J Mol Biol. 1980;143(2):161–78.

    Article  PubMed  CAS  Google Scholar 

  21. Myers EW. Toward simplifying and accurately formulating fragment assembly. J Comput Biol. 1995;2(2):275–90.

    Article  PubMed  CAS  Google Scholar 

  22. Zhi D, Raphael BJ, Price AL, Tang H, Pevzner PA. Identifying repeat domains in large genomes. Genome Biol. 2006;7(1):R7.

    Article  PubMed  Google Scholar 

  23. Perlis C, Herlyn M. Recent advances in melanoma biology. Oncologist. 2004;9(2):182–7.

    Article  PubMed  Google Scholar 

  24. Miller AJ, Mihm Jr MC. Melanoma. N Engl J Med. 2006;355(1):51–65.

    Article  PubMed  CAS  Google Scholar 

  25. Clark Jr WH, Elder DE, Guerry DT, Epstein MN, Greene MH, Van Horn M. A study of tumor progression: the precursor lesions of superficial spreading and nodular melanoma. Hum Pathol. 1984;15(12):1147–65.

    Article  PubMed  Google Scholar 

  26. Zembowicz A, Scolyer RA. Nevus/melanocytoma/melanoma: an emerging paradigm for classification of melanocytic neoplasms? Arch Pathol Lab Med. 2011;135(3):300–6.

    PubMed  Google Scholar 

  27. Uong A, Zon LI. Melanocytes in development and cancer. J Cell Physiol. 2010;222(1):38–41.

    Article  PubMed  CAS  Google Scholar 

  28. Chin L, Garraway LA, Fisher DE. Malignant melanoma: genetics and therapeutics in the genomic era. Genes Dev. 2006;20(16):2149–82.

    Article  PubMed  CAS  Google Scholar 

  29. Satyamoorthy K, Li G, Gerrero MR, et al. Constitutive mitogen-activated protein kinase activation in melanoma is mediated by both BRAF mutations and autocrine growth factor stimulation. Cancer Res. 2003;63(4):756–9.

    PubMed  CAS  Google Scholar 

  30. Willmore-Payne C, Holden JA, Tripp S, Layfield LJ. Human malignant melanoma: detection of BRAF- and c-kit-activating mutations by high-resolution amplicon melting analysis. Hum Pathol. 2005;36(5):486–93.

    Article  PubMed  CAS  Google Scholar 

  31. Ackermann J, Frutschi M, Kaloulis K, McKee T, Trumpp A, Beermann F. Metastasizing melanoma formation caused by expression of activated N-RasQ61K on an INK4a-deficient background. Cancer Res. 2005;65(10):4005–11.

    Article  PubMed  CAS  Google Scholar 

  32. Gray-Schopfer VC, da Rocha Dias S, Marais R. The role of B-RAF in melanoma. Cancer Metastasis Rev. 2005;24(1):165–83.

    Article  PubMed  CAS  Google Scholar 

  33. Spittle C, Ward MR, Nathanson KL, et al. Application of a BRAF pyrosequencing assay for mutation detection and copy number analysis in malignant melanoma. J Mol Diagn. 2007;9(4):464–71.

    Article  PubMed  CAS  Google Scholar 

  34. Greulich KM, Utikal J, Peter RU, Krahn G. c-MYC and nodular malignant melanoma. A case report. Cancer. 2000;89(1):97–103.

    Article  PubMed  CAS  Google Scholar 

  35. Bastian BC, Olshen AB, LeBoit PE, Pinkel D. Classifying melanocytic tumors based on DNA copy number changes. Am J Pathol. 2003;163(5):1765–70.

    Article  PubMed  CAS  Google Scholar 

  36. Cowan JM, Halaban R, Francke U. Cytogenetic analysis of melanocytes from premalignant nevi and melanomas. J Natl Cancer Inst. 1988;80(14):1159–64.

    Article  PubMed  CAS  Google Scholar 

  37. Carr KM, Bittner M, Trent JM. Gene-expression profiling in human cutaneous melanoma. Oncogene. 2003;22(20):3076–80.

    Article  PubMed  CAS  Google Scholar 

  38. Haqq C, Nosrati M, Sudilovsky D, et al. The gene expression signatures of melanoma progression. Proc Natl Acad Sci U S A. 2005;102(17):6092–7.

    Article  PubMed  CAS  Google Scholar 

  39. Smith AP, Hoek K, Becker D. Whole-genome expression profiling of the melanoma progression pathway reveals marked molecular differences between nevi/melanoma in situ and advanced-stage melanomas. Cancer Biol Ther. 2005;4(9):1018–29.

    Article  PubMed  CAS  Google Scholar 

  40. Jaeger J, Koczan D, Thiesen HJ, et al. Gene expression signatures for tumor progression, tumor subtype, and tumor thickness in laser-microdissected melanoma tissues. Clin Cancer Res. 2007;13(3):806–15.

    Article  PubMed  CAS  Google Scholar 

  41. Riker AI, Enkemann SA, Fodstad O, et al. The gene expression profiles of primary and metastatic melanoma yields a transition point of tumor progression and metastasis. BMC Med Genomics. 2008;1:13.

    Article  PubMed  Google Scholar 

  42. Alonso SR, Tracey L, Ortiz P, et al. A high-throughput study in melanoma identifies epithelial-mesenchymal transition as a major determinant of metastasis. Cancer Res. 2007;67(7):3450–60.

    Article  PubMed  CAS  Google Scholar 

  43. John T, Black MA, Toro TT, et al. Predicting clinical outcome through molecular profiling in stage III melanoma. Clin Cancer Res. 2008;14(16):5173–80.

    Article  PubMed  CAS  Google Scholar 

  44. Karim RZ, Li W, Sanki A, et al. Reduced p16 and increased cyclin D1 and pRb expression are correlated with progression in cutaneous melanocytic tumors. Int J Surg Pathol. 2009;17(5):361–7.

    Article  PubMed  Google Scholar 

  45. Mehnert JM, McCarthy MM, Jilaveanu L, et al. Quantitative expression of VEGF, VEGF-R1, VEGF-R2, and VEGF-R3 in melanoma tissue microarrays. Hum Pathol. 2010;41(3):375–84.

    Article  PubMed  CAS  Google Scholar 

  46. DeRisi J, Penland L, Brown PO, et al. Use of a cDNA microarray to analyse gene expression patterns in human cancer. Nat Genet. 1996;14(4):457–60.

    Article  PubMed  CAS  Google Scholar 

  47. el-Deiry WS, Tokino T, Velculescu VE, et al. WAF1, a potential mediator of p53 tumor suppression. Cell. 1993;75(4):817–25.

    Article  PubMed  CAS  Google Scholar 

  48. Graves DT, Barnhill R, Galanopoulos T, Antoniades HN. Expression of monocyte chemotactic protein-1 in human melanoma in vivo. Am J Pathol. 1992;140(1):9–14.

    PubMed  CAS  Google Scholar 

  49. Vijayasaradhi S, Doskoch PM, Wolchok J, Houghton AN. Melanocyte differentiation marker gp75, the brown locus protein, can be regulated independently of tyrosinase and pigmentation. J Invest Dermatol. 1995;105(1):113–9.

    Article  PubMed  CAS  Google Scholar 

  50. Bittner M, Meltzer P, Chen Y, et al. Molecular classification of cutaneous malignant melanoma by gene expression profiling. Nature. 2000;406(6795):536–40.

    Article  PubMed  CAS  Google Scholar 

  51. Kabbarah O, Nogueira C, Feng B, et al. Integrative genome comparison of primary and metastatic melanomas. PLoS One. 2010;5(5):e10770.

    Article  PubMed  Google Scholar 

  52. Morton DL, Wen DR, Wong JH, et al. Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg. 1992;127(4):392–9.

    Article  PubMed  CAS  Google Scholar 

  53. Yu LL, Flotte TJ, Tanabe KK, et al. Detection of microscopic melanoma metastases in sentinel lymph nodes. Cancer. 1999;86(4):617–27.

    Article  PubMed  CAS  Google Scholar 

  54. Messina JL, Glass LF, Cruse CW, Berman C, Ku NK, Reintgen DS. Pathologic examination of the sentinel lymph node in malignant melanoma. Am J Surg Pathol. 1999;23(6):686–90.

    Article  PubMed  CAS  Google Scholar 

  55. Koh SS, Opel ML, Wei JP, et al. Molecular classification of melanomas and nevi using gene expression microarray signatures and formalin-fixed and paraffin-embedded tissue. Mod Pathol. 2009;22(4):538–46.

    Article  PubMed  CAS  Google Scholar 

  56. Seftor EA, Brown KM, Chin L, et al. Epigenetic transdifferentiation of normal melanocytes by a metastatic melanoma microenvironment. Cancer Res. 2005;65(22):10164–9.

    Article  PubMed  CAS  Google Scholar 

  57. Hoon DS, Spugnardi M, Kuo C, Huang SK, Morton DL, Taback B. Profiling epigenetic inactivation of tumor suppressor genes in tumors and plasma from cutaneous melanoma patients. Oncogene. 2004;23(22):4014–22.

    Article  PubMed  CAS  Google Scholar 

  58. Furuta J, Nobeyama Y, Umebayashi Y, Otsuka F, Kikuchi K, Ushijima T. Silencing of Peroxiredoxin 2 and aberrant methylation of 33 CpG islands in putative promoter regions in human malignant melanomas. Cancer Res. 2006;66(12):6080–6.

    Article  PubMed  CAS  Google Scholar 

  59. Liu S, Ren S, Howell P, Fodstad O, Riker AI. Identification of novel epigenetically modified genes in human melanoma via promoter methylation gene profiling. Pigment Cell Melanoma Res. 2008;21(5):545–58.

    Article  PubMed  CAS  Google Scholar 

  60. Rothhammer T, Bosserhoff AK. Epigenetic events in malignant melanoma. Pigment Cell Res. 2007;20(2):92–111.

    Article  PubMed  CAS  Google Scholar 

  61. Muthusamy V, Duraisamy S, Bradbury CM, et al. Epigenetic silencing of novel tumor suppressors in malignant melanoma. Cancer Res. 2006;66(23):11187–93.

    Article  PubMed  CAS  Google Scholar 

  62. Stark MS, Tyagi S, Nancarrow DJ, et al. Characterization of the melanoma miRNAome by deep sequencing. PLoS One. 2010;5(3):e9685.

    Article  PubMed  Google Scholar 

  63. Winnepenninckx V, Lazar V, Michiels S, et al. Gene expression profiling of primary cutaneous melanoma and clinical outcome. J Natl Cancer Inst. 2006;98(7):472–82.

    Article  PubMed  CAS  Google Scholar 

  64. Eisen T, Ahmad T, Flaherty KT, et al. Sorafenib in advanced melanoma: a phase II randomised discontinuation trial analysis. Br J Cancer. 2006;95(5):581–6.

    Article  PubMed  CAS  Google Scholar 

  65. Bedikian AY, Millward M, Pehamberger H, et al. Bcl-2 antisense (oblimersen sodium) plus dacarbazine in patients with advanced melanoma: the Oblimersen Melanoma Study Group. J Clin Oncol. 2006;24(29):4738–45.

    Article  PubMed  CAS  Google Scholar 

  66. Markovic SN, Geyer SM, Dawkins F, et al. A phase II study of bortezomib in the treatment of metastatic malignant melanoma. Cancer. 2005;103(12):2584–9.

    Article  PubMed  CAS  Google Scholar 

  67. End DW, Smets G, Todd AV, et al. Characterization of the antitumor effects of the selective farnesyl protein transferase inhibitor R115777 in vivo and in vitro. Cancer Res. 2001;61(1):131–7.

    PubMed  CAS  Google Scholar 

  68. O’Donnell A, Faivre S, Burris 3rd HA, et al. Phase I pharmacokinetic and pharmacodynamic study of the oral mammalian target of rapamycin inhibitor everolimus in patients with advanced solid tumors. J Clin Oncol. 2008;26(10):1588–95.

    Article  PubMed  Google Scholar 

Download references

Acknowledgement

We are grateful to Anna Maria Aliperti for her assistance in the editing of the manuscript.

Author information

Authors and Affiliations

  1. Institute of Genetics and Biophysics, I.G.B., A.Buzzati-Traverso, CNR, Via Pierto Castellino, 111, Naples, Italy

    Stefania Crispi PhD

  2. Department of Genetics and Biophysics, Institute of Genetics and Biophysics, Naples, Italy

    Emilia Caputo

Authors
  1. Stefania Crispi PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Emilia Caputo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stefania Crispi PhD .

Editor information

Editors and Affiliations

  1. and Pharmaceutical Sciences and Technologies, Second University of Naples Department of Environmental, Biological, Naples, Italy

    Alfonso Baldi

  2. Department of Dermatology, Pius Hospital de Valls, Valls, Tarragona, Spain

    Paola Pasquali

  3. S.A.F.U. Department, Regina Elena Cancer Institute, Rome, Italy

    Enrico P Spugnini

Glossary

ALM

Acral lentiginous melanoma, a melanoma subtype not associated with UV exposure

Cye3 and Cy5

Fluorescent dyes belonging to the cyanine dye family

Gbp

Giga base pairs, one billion pairs of DNA nucleotide bases

GWA

Genome-wide association

LMM

Lentigo maligna melanoma, a melanoma subtype associated with chronic sun exposure

MM

Metastatic melanoma

NGS

Next-generation sequencing

NHEM

Normal human epidermal melanocytes

PCM

Primary cutaneous melanoma

RGP

Radial growth phase melanoma

SSM

Superficial spreading melanoma, a melanoma subtype linked to severe sunburns

TMA

Tissue microarray

VGP

Vertical growth phase melanoma

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this chapter

Cite this chapter

Crispi, S., Caputo, E. (2014). Gene Expression Profiling in Melanoma. In: Baldi, A., Pasquali, P., Spugnini, E. (eds) Skin Cancer. Current Clinical Pathology. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4614-7357-2_36

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-7357-2_36

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4614-7356-5

  • Online ISBN: 978-1-4614-7357-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation