Skip to main content

Proteomics Methods

  • Chapter
  • First Online:
Molecular Pathology in Cancer Research

Abstract

Proteins play many roles in regulating the biochemistry of cells and therefore in the maintenance of good health. Though the genome contains essential information, it is at the translational and post-translational level that many other vital mechanisms of cellular control are to be found. Proteins exhibit a wide range of chemical properties and are involved in many aspects of biological systems, e.g., structural, enzymic catalysis, hormonal and other signalling processes. It is important to both identify and quantify the proteins that are key to understanding a particular pathology. In this chapter the methods used to achieve this are described.

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

Access this chapter

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

Abbreviations

2DPAGE:

Two dimensional polyacrylamide gel electrophoresis

CSF:

Cerebrospinal fluid

CVF:

Cervico vaginal fluid

DIGE:

Fluorescent difference gel electrophoresis

ELISA:

Enzyme linked immunosorbent assay

IHC:

Immunohistochemistry

MALDI-MS:

Matrix assisted laser desorption ionization mass spectrometry

PCR:

Polymerase chain reaction

RIA:

Radioimmunoassay

SDS-PAGE:

Sodium dodecyl sulphate polyacrylamide gel electrophoresis

WB:

Western Blotting

References

  1. Blonder J, Issaq HJ, Veenstra TD (2011) Proteomic biomarker discovery: it’s more than just mass spectrometry. Electrophoresis 32(13):1541–1548. doi:10.1002/elps.201000585

    CAS  PubMed  Google Scholar 

  2. Issaq HJ, Waybright TJ, Veenstra TD (2011) Cancer biomarker discovery: opportunities and pitfalls in analytical methods. Electrophoresis 32(9):967–975. doi:10.1002/elps.201000588

    Article  CAS  PubMed  Google Scholar 

  3. Wasinger VC, Cordwell SJ, Cerpa-Poljak A, Yan JX, Gooley AA, Wilkins MR, Duncan MW, Harris R, Williams KL, Humphery-Smith I (1995) Progress with gene-product mapping of the Mollicutes: Mycoplasma genitalium. Electrophoresis 16(7):1090–1094

    Article  CAS  PubMed  Google Scholar 

  4. Blackstock WP, Weir MP (1999) Proteomics: quantitative and physical mapping of cellular proteins. Trends Biotechnol 17(3):121–127

    Article  CAS  PubMed  Google Scholar 

  5. Deribe YL, Pawson T, Dikic I (2010) Post-translational modifications in signal integration. Nat Struct Mol Biol 17(6):666–672. doi:10.1038/nsmb.1842

    Article  CAS  PubMed  Google Scholar 

  6. Rifai N, Gillette MA, Carr SA (2006) Protein biomarker discovery and validation: the long and uncertain path to clinical utility. Nat Biotechnol 24(8):971–983. doi:10.1038/nbt1235

    Article  CAS  PubMed  Google Scholar 

  7. Whiteley G (2008) Bringing diagnostic technologies to the clinical laboratory: rigor, regulation, and reality. Proteomics Clin Appl 2(10-11):1378–1385. doi:10.1002/prca.200780170

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Liu X, Valentine SJ, Plasencia MD, Trimpin S, Naylor S, Clemmer DE (2007) Mapping the human plasma proteome by SCX-LC-IMS-MS. J Am Soc Mass Spectrom 18(7):1249–1264. doi:10.1016/j.jasms.2007.04.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Anderson NL, Polanski M, Pieper R, Gatlin T, Tirumalai RS, Conrads TP, Veenstra TD, Adkins JN, Pounds JG, Fagan R, Lobley A (2004) The human plasma proteome: a nonredundant list developed by combination of four separate sources. Mol Cell Proteomics 3(4):311–326. doi:10.1074/mcp.M300127-MCP200

    Article  CAS  PubMed  Google Scholar 

  10. Polanski M, Anderson NL (2007) A list of candidate cancer biomarkers for targeted proteomics. Biomark Insights 1:1–48

    PubMed  PubMed Central  Google Scholar 

  11. Randall SA, McKay MJ, Molloy MP (2010) Evaluation of blood collection tubes using selected reaction monitoring MS: implications for proteomic biomarker studies. Proteomics 10(10):2050–2056. doi:10.1002/pmic.200900517

    Article  CAS  PubMed  Google Scholar 

  12. Gorg A, Drews O, Luck C, Weiland F, Weiss W (2009) 2-DE with IPGs. Electrophoresis 30(Suppl 1):S122–S132. doi:10.1002/elps.200900051

    Article  PubMed  Google Scholar 

  13. Kaltschmidt E, Wittmann HG (1969) Ribosomal proteins: VI. Preparative polyacrylamide del electrophoresis as applied to the isolation of ribosomal proteins. Anal Biochem 30(1):132–141

    Article  CAS  PubMed  Google Scholar 

  14. O’Farrell PH (1975) High resolution two-dimensional electrophoresis of proteins. J Biol Chem 250(10):4007–4021

    PubMed  PubMed Central  Google Scholar 

  15. Perrot M, Sagliocco F, Mini T, Monribot C, Schneider U, Shevchenko A, Mann M, Jeno P, Boucherie H (1999) Two-dimensional gel protein database of Saccharomyces cerevisiae (update 1999). Electrophoresis 20(11):2280–2298. doi:10.1002/(SICI)1522-2683(19990801)20:11<2280::AID-ELPS2280>3.0.CO;2-Q

    Article  CAS  PubMed  Google Scholar 

  16. Shevchenko A, Jensen ON, Podtelejnikov AV, Sagliocco F, Wilm M, Vorm O, Mortensen P, Boucherie H, Mann M (1996) Linking genome and proteome by mass spectrometry: large-scale identification of yeast proteins from two dimensional gels. Proc Natl Acad Sci U S A 93(25):14440–14445

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Unlu M, Morgan ME, Minden JS (1997) Difference gel electrophoresis: a single gel method for detecting changes in protein extracts. Electrophoresis 18(11):2071–2077. doi:10.1002/elps.1150181133

    Article  CAS  PubMed  Google Scholar 

  18. Alban A, David SO, Bjorkesten L, Andersson C, Sloge E, Lewis S, Currie I (2003) A novel experimental design for comparative two-dimensional gel analysis: two-dimensional difference gel electrophoresis incorporating a pooled internal standard. Proteomics 3(1):36–44. doi:10.1002/pmic.200390006

    Article  CAS  PubMed  Google Scholar 

  19. Gauci VJ, Wright EP, Coorssen JR (2011) Quantitative proteomics: assessing the spectrum of in-gel protein detection methods. J Chem Biol 4(1):3–29. doi:10.1007/s12154-010-0043-5

    Article  PubMed  Google Scholar 

  20. Sabido E, Selevsek N, Aebersold R (2011) Mass spectrometry-based proteomics for systems biology. Curr Opin Biotechnol. doi:10.1016/j.copbio.2011.11.014

    PubMed  Google Scholar 

  21. Shevchenko A, Tomas H, Havlis J, Olsen JV, Mann M (2006) In-gel digestion for mass spectrometric characterization of proteins and proteomes. Nat Protoc 1(6):2856–2860. doi:10.1038/Nprot.2006.468

    Google Scholar 

  22. LeGendre N (1990) Immobilon-P transfer membrane: applications and utility in protein biochemical analysis. Biotechniques 9(6 Suppl):788–805

    CAS  PubMed  Google Scholar 

  23. Towbin H, Staehelin T, Gordon J (1979) Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A 76(9):4350–4354

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Kurien BT, Dorri Y, Dillon S, Dsouza A, Scofield RH (2011) An overview of Western blotting for determining antibody specificities for immunohistochemistry. Methods Mol Biol 717:55–67. doi:10.1007/978-1-61779-024-9_3

    Article  CAS  PubMed  Google Scholar 

  25. Yalow RS, Berson SA (1959) Assay of plasma insulin in human subjects by immunological methods. Nature 184(4699):1648–1649

    Article  CAS  PubMed  Google Scholar 

  26. Wu AHB (2006) A selected history and future of immunoassay development and applications in clinical chemistry. Clin Chim Acta 369(2):119–124. doi:10.1016/J.Cca.2006.02.045

    Google Scholar 

  27. Hu SH, Xie Z, Qian J, Blackshaw S, Zhu H (2011) Functional protein microarray technology. Wires Syst Biol Med 3(3):255–268. doi:10.1002/Wsbm.118

    Google Scholar 

  28. Joos T, Bachmann J (2009) Protein microarrays: potentials and limitations. Front Biosci 14:4376–4385

    Article  CAS  Google Scholar 

  29. Yu X, Schneiderhan-Marra N, Hsu HY, Bachmann J, Joos TO (2009) Protein microarrays: effective tools for the study of inflammatory diseases. Methods Mol Biol 577:199–214. doi:10.1007/978-1-60761-232-2_15

    Article  CAS  PubMed  Google Scholar 

  30. Katz C, Levy-Beladev L, Rotem-Bamberger S, Rito T, Rudiger SG, Friedler A (2011) Studying protein-protein interactions using peptide arrays. Chem Soc Rev 40(5):2131–2145. doi:10.1039/c0cs00029a

    Article  CAS  PubMed  Google Scholar 

  31. Winkler DF, Hilpert K, Brandt O, Hancock RE (2009) Synthesis of peptide arrays using SPOT-technology and the CelluSpots-method. Methods Mol Biol 570:157–174. doi:10.1007/978-1-60327-394-7_5

    Article  CAS  PubMed  Google Scholar 

  32. Sanchez-Carbayo M (2011) Antibody microarrays as tools for biomarker discovery. Methods Mol Biol 785:159–182. doi:10.1007/978-1-61779-286-1_11

    Article  CAS  PubMed  Google Scholar 

  33. Rice GE, Georgiou HM, Ahmed N, Shi G, Kruppa G (2006) Translational proteomics: developing a predictive capacity – a review. Placenta 27 Suppl A:S76–S86. doi:10.1016/j.placenta.2005.11.003

    Google Scholar 

  34. Coons AH, Creech HJ, Jones RN, Berliner E (1942) The demonstration of pneumococcal antigen in tissues by the use of fluorescent antibody. J Immunol 45(3):159–170

    CAS  Google Scholar 

  35. Abbondanzo SL (1999) Paraffin immunohistochemistry as an adjunct to hematopathology. Ann Diagn Pathol 3(5):318–327. doi:10.1053/ADPA00300318

    Article  CAS  PubMed  Google Scholar 

  36. Shi SR, Shi Y, Taylor CR (2011) Antigen retrieval immunohistochemistry: review and future prospects in research and diagnosis over two decades. J Histochem Cytochem 59(1):13–32. doi:10.1369/jhc.2010.957191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Taylor CR (2011) New revised Clinical and Laboratory Standards Institute Guidelines for Immunohistochemistry and Immunocytochemistry. Appl Immunohistochem Mol Morphol 19(4):289–290. doi:10.1097/PAI.0b013e31821b505b

    Google Scholar 

  38. Shushan B (2010) A review of clinical diagnostic applications of liquid chromatography-tandem mass spectrometry. Mass Spectrom Rev 29(6):930–44. doi:10.1002/mas.20295

    Google Scholar 

  39. Stevenson LG, Drake SK, Murray PR (2010) Rapid identification of bacteria in positive blood culture broths by matrix-assisted laser desorption ionization-time of flight mass spectrometry. J Clin Microbiol 48(2):444–447. doi:10.1128/JCM.01541-09

    Article  CAS  PubMed  Google Scholar 

  40. Parker CE, Pearson TW, Anderson NL, Borchers CH (2010) Mass-spectrometry-based clinical proteomics—a review and prospective. Analyst 135(8):1830–1838. doi:10.1039/c0an00105h

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Fenn JB (2003) Electrospray wings for molecular elephants (Nobel lecture). Angew Chem Int Ed Engl 42(33):3871–3894. doi:10.1002/anie.200300605

    Article  CAS  PubMed  Google Scholar 

  42. Fenn JB, Mann M, Meng CK, Wong SF, Whitehouse CM (1989) Electrospray ionization for mass spectrometry of large biomolecules. Science 246(4926):64–71

    Article  CAS  PubMed  Google Scholar 

  43. Hillenkamp F, Karas M (1990) Mass spectrometry of peptides and proteins by matrix-assisted ultraviolet laser desorption/ionization. Methods Enzymol 193:280–295

    Article  CAS  PubMed  Google Scholar 

  44. Karas M, Hillenkamp F (1988) Laser desorption ionization of proteins with molecular masses exceeding 10,000 daltons. Anal Chem 60(20):2299–2301

    Article  CAS  PubMed  Google Scholar 

  45. Jungblut PR, Schluter H (2011) Towards the analysis of protein species: an overview about strategies and methods. Amino Acids 41(2):219–222. doi:10.1007/s00726-010-0828-4

    Article  CAS  PubMed  Google Scholar 

  46. Hunt T, Huang Y, Ross P, Pillai S, Purkayastha S, Pappin D (2004) Protein expression analysis and biomarker identification and quantification using multiplexed isobaric tagging technology – iTRAQ reagents. Mol Cell Proteomics 3(10):S286

    Google Scholar 

  47. Dayon L, Hainard A, Licker V, Turck N, Kuhn K, Hochstrasser DF, Burkhard PR, Sanchez JC (2008) Relative quantification of proteins in human cerebrospinal fluids by MS/MS using 6-plex isobaric tags. Anal Chem 80(8):2921–2931. doi:10.1021/ac702422x

    Article  CAS  PubMed  Google Scholar 

  48. Ashman K, Ruppen Canas MI, Luque-Garcia JL, Garcia Martinez F (2011) Stable isotopic labeling for proteomics. In: Sample preparation in biological mass spectrometry. doi:10.1007/978-94-007-0828-0_27

    Google Scholar 

  49. Coombs KM (2011) Quantitative proteomics of complex mixtures. Expert Rev Proteomics 8(5):659–677. doi:10.1586/epr.11.55

    Article  CAS  PubMed  Google Scholar 

  50. Monetti M, Nagaraj N, Sharma K, Mann M (2011) Large-scale phosphosite quantification in tissues by a spike-in SILAC method. Nat Methods 8(8):U655–U674. doi:10.1038/Nmeth.1647

    Google Scholar 

  51. Ong SE, Blagoev B, Kratchmarova I, Kristensen DB, Steen H, Pandey A, Mann M (2002) Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics. Mol Cell Proteomics 1(5):376–386. doi:10.1074/Mcp.M200025-Mcp200

    Google Scholar 

  52. Rauh M (2012) LC-MS/MS for protein and peptide quantification in clinical chemistry. J Chromatogr B Analyt Technol Biomed Life Sci 883–884:59–67. doi:10.1016/j.jchromb.2011.09.030

    Article  PubMed  Google Scholar 

  53. Farrah T, Deutsch EW, Kreisberg R, Sun Z, Campbell DS, Mendoza L, Kusebauch U, Brusniak MY, Huttenhain R, Schiess R, Selevsek N, Aebersold R, Moritz RL (2012) PASSEL: The PeptideAtlas SRM Experiment Library. Proteomics. doi:10.1002/pmic.201100515

    Google Scholar 

  54. Ciccimaro E, Blair IA (2010) Stable-isotope dilution LC-MS for quantitative biomarker analysis. Bioanalysis 2(2):311–341. doi:10.4155/bio.09.185

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Anderson NL, Anderson NG, Haines LR, Hardie DB, Olafson RW, Pearson TW (2004) Mass spectrometric quantitation of peptides and proteins using Stable Isotope Standards and Capture by Anti-Peptide Antibodies (SISCAPA). J Proteome Res 3(2):235–244

    Article  CAS  PubMed  Google Scholar 

  56. Whiteaker JR, Zhao L, Anderson L, Paulovich AG (2009) An automated and multiplexed method for high throughput peptide immunoaffinity enrichment and multiple reaction monitoring mass spectrometry-based quantification of protein biomarkers. Mol Cell Proteomics. doi:10.1074/mcp.M900254-MCP200. pii: M900254-MCP200

    Google Scholar 

  57. Addona TA, Abbatiello SE, Schilling B, Skates SJ, Mani DR, Bunk DM, Spiegelman CH, Zimmerman LJ, Ham AJL, Keshishian H, Hall SC, Allen S, Blackman RK, Borchers CH, Buck C, Cardasis HL, Cusack MP, Dodder NG, Gibson BW, Held JM, Hiltke T, Jackson A, Johansen EB, Kinsinger CR, Li J, Mesri M, Neubert TA, Niles RK, Pulsipher TC, Ransohoff D, Rodriguez H, Rudnick PA, Smith D, Tabb DL, Tegeler TJ, Variyath AM, Vega-Montoto LJ, Wahlander A, Waldemarson S, Wang M, Whiteaker JR, Zhao L, Anderson NL, Fisher SJ, Liebler DC, Paulovich AG, Regnier FE, Tempst P, Carr SA (2009) Multi-site assessment of the precision and reproducibility of multiple reaction monitoring-based measurements of proteins in plasma (vol 27, pg 633, 2009). Nat Biotechnol 27(9):864. doi:10.1038/Nbt0909-864b

    Article  CAS  Google Scholar 

  58. Anderson NL, Jackson A, Smith D, Hardie D, Borchers C, Pearson TW (2009) SISCAPA peptide enrichment on magnetic beads using an in-line bead trap device. Mol Cell Proteomics 8(5):995–1005. doi:10.1074/Mcp.M800446-Mcp200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Dissmeyer N, Schnittger A (2011) The age of protein kinases. Methods Mol Biol 779:7–52. doi:10.1007/978-1-61779-264-9_2

    Article  CAS  PubMed  Google Scholar 

  60. Pawson T, Kofler M (2009) Kinome signaling through regulated protein-protein interactions in normal and cancer cells. Curr Opin Cell Biol 21(2):147–153. doi:10.1016/j.ceb.2009.02.005

    Article  CAS  PubMed  Google Scholar 

  61. Malumbres M, Barbacid M (2009) Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer 9(3):153–166. doi:10.1038/nrc2602

    Article  CAS  PubMed  Google Scholar 

  62. Iwai LK, Benoist C, Mathis D, White FM (2010) Quantitative phosphoproteomic analysis of T cell receptor signaling in diabetes prone and resistant mice. J Proteome Res 9(6):3135–3145. doi:10.1021/pr100035b

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Thingholm TE, Jensen ON, Larsen MR (2009) Analytical strategies for phosphoproteomics. Proteomics 9(6):1451–1468. doi:10.1002/pmic.200800454

    Article  CAS  PubMed  Google Scholar 

  64. Cazares LH, Troyer DA, Wang B, Drake RR, Semmes OJ (2011) MALDI tissue imaging: from biomarker discovery to clinical applications. Anal Bioanal Chem 401(1):17–27. doi:10.1007/s00216-011-5003-6

    Google Scholar 

  65. Vestal ML (2009) Modern MALDI time-of-flight mass spectrometry. J Mass Spectrom 44(3):303–317. doi:10.1002/jms.1537

    Article  CAS  PubMed  Google Scholar 

  66. Bandura DR, Baranov VI, Ornatsky OI, Antonov A, Kinach R, Lou X, Pavlov S, Vorobiev S, Dick JE, Tanner SD (2009) Mass cytometry: technique for real time single cell multitarget immunoassay based on inductively coupled plasma time-of-flight mass spectrometry. Anal Chem 81(16):6813–6822. doi:10.1021/ac901049w

    Article  CAS  PubMed  Google Scholar 

  67. Bendall SC, Simonds EF, Qiu P, el Amir AD, Krutzik PO, Finck R, Bruggner RV, Melamed R, Trejo A, Ornatsky OI, Balderas RS, Plevritis SK, Sachs K, Pe’er D, Tanner SD, Nolan GP (2011) Single-cell mass cytometry of differential immune and drug responses across a human hematopoietic continuum. Science 332(6030):687–696. doi:10.1126/science.1198704

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Janes MR, Rommel C (2011) Next-generation flow cytometry. Nat Biotechnol 29(7):602–604. doi:10.1038/nbt.1919

    Article  CAS  PubMed  Google Scholar 

  69. Ryzhov V, Fenselau C (2001) Characterization of the protein subset desorbed by MALDI from whole bacterial cells. Anal Chem 73(4):746–50

    Google Scholar 

  70. Fenselau C, Demirev PA (2001) Characterization of intact microorganisms by MALDI mass spectrometry. Mass Spectrom Rev 20(4):157–171. doi:10.1002/mas.10004

    Article  CAS  PubMed  Google Scholar 

  71. Holland RD, Wilkes JG, Rafii F, Sutherland JB, Persons CC, Voorhees KJ, Lay JO Jr (1996) Rapid identification of intact whole bacteria based on spectral patterns using matrix-assisted laser desorption/ionization with time-of-flight mass spectrometry. Rapid Commun Mass Spectrom 10(10):1227–1232. doi:10.1002/(SICI)1097-0231(19960731)10:10<1227::AID-RCM659>3.0.CO;2-6

    Article  CAS  PubMed  Google Scholar 

  72. Kathiresan S, Gona P, Larson MG, Vita JA, Mitchell GF, Tofler GH, Levy D, Newton-Cheh C, Wang TJ, Benjamin EJ, Vasan RS (2006) Cross-sectional relations of multiple biomarkers from distinct biological pathways to brachial artery endothelial function. Circulation 113(7):938–945. doi:10.1161/CIRCULATIONAHA.105.580233

    Article  CAS  PubMed  Google Scholar 

  73. Wang TJ, Gona P, Larson MG, Tofler GH, Levy D, Newton-Cheh C, Jacques PF, Rifai N, Selhub J, Robins SJ, Benjamin EJ, D’Agostino RB, Vasan RS (2006) Multiple biomarkers for the prediction of first major cardiovascular events and death. N Engl J Med 355(25):2631–2639. doi:10.1056/NEJMoa055373

    Article  CAS  PubMed  Google Scholar 

  74. Mor G, Visintin I, Lai Y, Zhao H, Schwartz P, Rutherford T, Yue L, Bray-Ward P, Ward DC (2005) Serum protein markers for early detection of ovarian cancer. Proc Natl Acad Sci U S A 102(21):7677–7682. doi:10.1073/pnas.0502178102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Georgiou HM, Lappas M, Georgiou GM, Marita A, Bryant VJ, Hiscock R, Permezel M, Khalil Z, Rice GE (2008) Screening for biomarkers predictive of gestational diabetes mellitus. Acta Diabetol 45(3):157–165. doi:10.1007/s00592-008-0037-8

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

KA acknowledges and thanks the Rotary Club of Williamstown, Victoria, Australia for partial salary support through the RoCan program

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Keith Ashman or Greg Rice .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media LLC

About this chapter

Cite this chapter

Ashman, K., Rice, G., Mitchell, M. (2016). Proteomics Methods. In: Lakhani, S., Fox, S. (eds) Molecular Pathology in Cancer Research. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-6643-1_10

Download citation

Publish with us

Policies and ethics