Skip to main content

Cancer Gene Discovery: Past to Present

  • Protocol
  • First Online:
Cancer Driver Genes

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1907))

Abstract

Cancer is a complex disease that originates from genetic changes leading to multiple phenotypic manifestations that ultimately result in suffering and death from cancer. Attempts have been made to define the phenotypic and genetic “hallmarks” of cancer, but many of these “hallmarks” remain descriptive, while the underlying mechanisms responsible for these hallmarks remain elusive. For decades, cancer researchers have been methodically identifying the molecular mechanisms that result in tumor initiation, growth, metastases, and resistance to therapy. Great strides forward have been made and we are entering an era of “precision medicine” with the goal of treating each cancer based on its unique etiology. Increasingly, the decision to use targeted therapies and immunotherapies in the clinic is based on the genotype of the cancer being treated. For example, specific tyrosine kinase inhibitors are only prescribed to patients that express the tyrosine kinase protein on their cancer cells. Likewise, a genetically unstable cancer is predictive for successful immunotherapy. Knowledge of the specific genetic changes that result in overproduction of oncogenes and reduced production of tumor suppressors is crucial for advancing therapeutic options for cancer. The first chapter of this book presents a brief history of cancer gene discovery. In the remaining chapters of this book, we present protocols using in silico, in vitro, and in vivo techniques for identifying genetic drivers of cancer, in the hope that these protocols will be used to increase our knowledge of the molecular mechanisms driving cancer.

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

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
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. Howlader N, Noone AM, Krapcho M, Miller D, Bishop K, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds) (2017) SEER Cancer Statistics Review, 1975-2014. National Cancer Institute, Bethesda, MD https://seer.cancer.gov/csr/1975_2014/

    Google Scholar 

  2. Harrow J, Frankish A, Gonzalez JM, Tapanari E, Diekhans M, Kokocinski F, Aken BL, Barrell D, Zadissa A, Searle S, Barnes I, Bignell A, Boychenko V, Hunt T, Kay M, Mukherjee G, Rajan J, Despacio-Reyes G, Saunders G, Steward C, Harte R, Lin M, Howald C, Tanzer A, Derrien T, Chrast J, Walters N, Balasubramanian S, Pei B, Tress M, Rodriguez JM, Ezkurdia I, van Baren J, Brent M, Haussler D, Kellis M, Valencia A, Reymond A, Gerstein M, Guigo R, Hubbard TJ (2012) GENCODE: the reference human genome annotation for The ENCODE Project. Genome Res 22(9):1760–1774. https://doi.org/10.1101/gr.135350.111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Princiotta MF, Finzi D, Qian SB, Gibbs J, Schuchmann S, Buttgereit F, Bennink JR, Yewdell JW (2003) Quantitating protein synthesis, degradation, and endogenous antigen processing. Immunity 18(3):343–354

    Article  CAS  PubMed  Google Scholar 

  4. Huarte M (2015) The emerging role of lncRNAs in cancer. Nat Med 21(11):1253–1261. https://doi.org/10.1038/nm.3981

    Article  CAS  PubMed  Google Scholar 

  5. Vannini I, Fanini F, Fabbri M (2018) Emerging roles of microRNAs in cancer. Curr Opin Genet Dev 48:128–133. https://doi.org/10.1016/j.gde.2018.01.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Ecker JR, Bickmore WA, Barroso I, Pritchard JK, Gilad Y, Segal E (2012) Genomics: ENCODE explained. Nature 489(7414):52–55. https://doi.org/10.1038/489052a

    Article  CAS  PubMed  Google Scholar 

  7. Ley TJ, Mardis ER, Ding L, Fulton B, McLellan MD, Chen K, Dooling D, Dunford-Shore BH, McGrath S, Hickenbotham M, Cook L, Abbott R, Larson DE, Koboldt DC, Pohl C, Smith S, Hawkins A, Abbott S, Locke D, Hillier LW, Miner T, Fulton L, Magrini V, Wylie T, Glasscock J, Conyers J, Sander N, Shi X, Osborne JR, Minx P, Gordon D, Chinwalla A, Zhao Y, Ries RE, Payton JE, Westervelt P, Tomasson MH, Watson M, Baty J, Ivanovich J, Heath S, Shannon WD, Nagarajan R, Walter MJ, Link DC, Graubert TA, DiPersio JF, Wilson RK (2008) DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome. Nature 456(7218):66–72

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Govindan R, Ding L, Griffith M, Subramanian J, Dees ND, Kanchi KL, Maher CA, Fulton R, Fulton L, Wallis J, Chen K, Walker J, McDonald S, Bose R, Ornitz D, Xiong D, You M, Dooling DJ, Watson M, Mardis ER, Wilson RK (2012) Genomic landscape of non-small cell lung cancer in smokers and never-smokers. Cell 150(6):1121–1134. https://doi.org/10.1016/j.cell.2012.08.024

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Bass AJ, Lawrence MS, Brace LE, Ramos AH, Drier Y, Cibulskis K, Sougnez C, Voet D, Saksena G, Sivachenko A, Jing R, Parkin M, Pugh T, Verhaak RG, Stransky N, Boutin AT, Barretina J, Solit DB, Vakiani E, Shao W, Mishina Y, Warmuth M, Jimenez J, Chiang DY, Signoretti S, Kaelin WG, Spardy N, Hahn WC, Hoshida Y, Ogino S, Depinho RA, Chin L, Garraway LA, Fuchs CS, Baselga J, Tabernero J, Gabriel S, Lander ES, Getz G, Meyerson M (2011) Genomic sequencing of colorectal adenocarcinomas identifies a recurrent VTI1A-TCF7L2 fusion. Nat Genet 43:964–968. https://doi.org/10.1038/ng.936

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Ren S, Wei GH, Liu D, Wang L, Hou Y, Zhu S, Peng L, Zhang Q, Cheng Y, Su H, Zhou X, Zhang J, Li F, Zheng H, Zhao Z, Yin C, He Z, Gao X, Zhau HE, Chu CY, Wu JB, Collins C, Volik SV, Bell R, Huang J, Wu K, Xu D, Ye D, Yu Y, Zhu L, Qiao M, Lee HM, Yang Y, Zhu Y, Shi X, Chen R, Wang Y, Xu W, Cheng Y, Xu C, Gao X, Zhou T, Yang B, Hou J, Liu L, Zhang Z, Zhu Y, Qin C, Shao P, Pang J, Chung LWK, Xu J, Wu CL, Zhong W, Xu X, Li Y, Zhang X, Wang J, Yang H, Wang J, Huang H, Sun Y (2017) Whole-genome and transcriptome sequencing of prostate cancer identify new genetic alterations driving disease progression. Eur Urol. https://doi.org/10.1016/j.eururo.2017.08.027

    Article  CAS  PubMed  Google Scholar 

  11. Nik-Zainal S, Davies H, Staaf J, Ramakrishna M, Glodzik D, Zou X, Martincorena I, Alexandrov LB, Martin S, Wedge DC, Van Loo P, Ju YS, Smid M, Brinkman AB, Morganella S, Aure MR, Lingjaerde OC, Langerod A, Ringner M, Ahn SM, Boyault S, Brock JE, Broeks A, Butler A, Desmedt C, Dirix L, Dronov S, Fatima A, Foekens JA, Gerstung M, Hooijer GK, Jang SJ, Jones DR, Kim HY, King TA, Krishnamurthy S, Lee HJ, Lee JY, Li Y, McLaren S, Menzies A, Mustonen V, O’Meara S, Pauporte I, Pivot X, Purdie CA, Raine K, Ramakrishnan K, Rodriguez-Gonzalez FG, Romieu G, Sieuwerts AM, Simpson PT, Shepherd R, Stebbings L, Stefansson OA, Teague J, Tommasi S, Treilleux I, Van den Eynden GG, Vermeulen P, Vincent-Salomon A, Yates L, Caldas C, Veer LV, Tutt A, Knappskog S, Tan BK, Jonkers J, Borg A, Ueno NT, Sotiriou C, Viari A, Futreal PA, Campbell PJ, Span PN, Van Laere S, Lakhani SR, Eyfjord JE, Thompson AM, Birney E, Stunnenberg HG, van de Vijver MJ, Martens JW, Borresen-Dale AL, Richardson AL, Kong G, Thomas G, Stratton MR (2016) Landscape of somatic mutations in 560 breast cancer whole-genome sequences. Nature 534:47–54. https://doi.org/10.1038/nature17676

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Pena-Llopis S, Vega-Rubin-de-Celis S, Liao A, Leng N, Pavia-Jimenez A, Wang S, Yamasaki T, Zhrebker L, Sivanand S, Spence P, Kinch L, Hambuch T, Jain S, Lotan Y, Margulis V, Sagalowsky AI, Summerour PB, Kabbani W, Wong SW, Grishin N, Laurent M, Xie XJ, Haudenschild CD, Ross MT, Bentley DR, Kapur P, Brugarolas J (2012) BAP1 loss defines a new class of renal cell carcinoma. Nat Genet 44(7):751–759. https://doi.org/10.1038/ng.2323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Futreal PA, Coin L, Marshall M, Down T, Hubbard T, Wooster R, Rahman N, Stratton MR (2004) A census of human cancer genes. Nat Rev Cancer 4(3):177–183

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Baxter JS, Leavy OC, Dryden NH, Maguire S, Johnson N, Fedele V, Simigdala N, Martin LA, Andrews S, Wingett SW, Assiotis I, Fenwick K, Chauhan R, Rust AG, Orr N, Dudbridge F, Haider S, Fletcher O (2018) Capture Hi-C identifies putative target genes at 33 breast cancer risk loci. Nat Commun 9(1):1028. https://doi.org/10.1038/s41467-018-03411-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Armitage P, Doll R (1954) The age distribution of cancer and a multi-stage theory of carcinogenesis. Br J Cancer 8(1):1–12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Knudson AG Jr (1971) Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A 68(4):820–823

    Article  PubMed  PubMed Central  Google Scholar 

  17. Tomasetti C, Marchionni L, Nowak MA, Parmigiani G, Vogelstein B (2015) Only three driver gene mutations are required for the development of lung and colorectal cancers. Proc Natl Acad Sci U S A 112(1):118–123. https://doi.org/10.1073/pnas.1421839112

    Article  CAS  PubMed  Google Scholar 

  18. Sud A, Kinnersley B, Houlston RS (2017) Genome-wide association studies of cancer: current insights and future perspectives. Nat Rev Cancer 17(11):692–704. https://doi.org/10.1038/nrc.2017.82

    Article  CAS  PubMed  Google Scholar 

  19. Rous P (1911) A sarcoma of the fowl transmissible by an agent separable from the tumor cells. J Exp Med 13:397–411

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Huebner RJ, Todaro GJ (1969) Oncogenes of RNA tumor viruses as determinants of cancer. Proc Natl Acad Sci U S A 64(3):1087–1094

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Gross L (1970) Viral etiology of cancer, leukemia and allied diseases. CA Cancer J Clin 20(4):242–247

    Article  CAS  PubMed  Google Scholar 

  22. Duesberg PH, Kawai S, Wang LH, Vogt PK, Murphy HM, Hanafusa H (1975) RNA of replication-defective strains of Rous sarcoma virus. Proc Natl Acad Sci U S A 72(4):1569–1573

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Stehelin D, Varmus HE, Bishop JM, Vogt PK (1976) DNA related to the transforming gene(s) of avian sarcoma viruses is present in normal avian DNA. Nature 260(5547):170–173

    Article  CAS  PubMed  Google Scholar 

  24. Wang LH, Duesberg PH, Kawai S, Hanafusa H (1976) Location of envelope-specific and sarcoma-specific oligonucleotides on RNA of Schmidt-Ruppin Rous sarcoma virus. Proc Natl Acad Sci U S A 73(2):447–451

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Tabin CJ, Bradley SM, Bargmann CI, Weinberg RA, Papageorge AG, Scolnick EM, Dhar R, Lowy DR, Chang EH (1982) Mechanism of activation of a human oncogene. Nature 300(5888):143–149

    Article  CAS  PubMed  Google Scholar 

  26. Parada LF, Tabin CJ, Shih C, Weinberg RA (1982) Human EJ bladder carcinoma oncogene is homologue of Harvey sarcoma virus ras gene. Nature 297(5866):474–478

    Article  CAS  PubMed  Google Scholar 

  27. Shih C, Weinberg RA (1982) Isolation of a transforming sequence from a human bladder carcinoma cell line. Cell 29(1):161–169

    Article  CAS  PubMed  Google Scholar 

  28. Duesberg PH, Vogt PK (1979) Avian acute leukemia viruses MC29 and MH2 share specific RNA sequences: evidence for a second class of transforming genes. Proc Natl Acad Sci U S A 76(4):1633–1637

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Hu SS, Lai MM, Vogt PK (1979) Genome of avian myelocytomatosis virus MC29: analysis by heteroduplex mapping. Proc Natl Acad Sci U S A 76(3):1265–1268

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Sheiness D, Bishop JM (1979) DNA and RNA from uninfected vertebrate cells contain nucleotide sequences related to the putative transforming gene of avian myelocytomatosis virus. J Virol 31(2):514–521

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Nunn MF, Seeburg PH, Moscovici C, Duesberg PH (1983) Tripartite structure of the avian erythroblastosis virus E26 transforming gene. Nature 306(5941):391–395

    Article  CAS  PubMed  Google Scholar 

  32. Leprince D, Saule S, de Taisne C, Gegonne A, Begue A, Righi M, Stehelin D (1983) The human DNA locus related to the oncogene myb of avian myeloblastosis virus (AMV): molecular cloning and structural characterization. EMBO J 2(7):1073–1078

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Frankel AE, Gilbert JH, Porzig KJ, Scolnick EM, Aaronson SA (1979) Nature and distribution of feline sarcoma virus nucleotide sequences. J Virol 30(3):821–827

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Donner L, Fedele LA, Garon CF, Anderson SJ, Sherr CJ (1982) McDonough feline sarcoma virus: characterization of the molecularly cloned provirus and its feline oncogene (v-fms). J Virol 41(2):489–500

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Cavalieri F, Ruscio T, Tinoco R, Benedict S, Davis C, Vogt PK (1985) Isolation of three new avian sarcoma viruses: ASV 9, ASV 17, and ASV 25. Virology 143(2):680–683

    Article  CAS  PubMed  Google Scholar 

  36. Maki Y, Bos TJ, Davis C, Starbuck M, Vogt PK (1987) Avian sarcoma virus 17 carries the jun oncogene. Proc Natl Acad Sci U S A 84(9):2848–2852

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Boveri T (2008) Concerning the origin of malignant tumours by Theodor Boveri. Translated and annotated by Henry Harris. J Cell Sci 121 (Supplement 1):1-84. https://doi.org/10.1242/jcs.025742

    Article  PubMed  Google Scholar 

  38. Friend SH, Bernards R, Rogelj S, Weinberg RA, Rapaport JM, Albert DM, Dryja TP (1986) A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature 323(6089):643–646

    Article  CAS  PubMed  Google Scholar 

  39. Weinberg RA (1998) One renegade cell : how cancer begins, 1st edn. Basic Books, New York, NY

    Google Scholar 

  40. Mukherjee S (2010) The Emperor of all maladies. Scribner, New York

    Google Scholar 

  41. Altshuler D, Daly MJ, Lander ES (2008) Genetic mapping in human disease. Science 322(5903):881–888. https://doi.org/10.1126/science.1156409

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Kinzler KW, Nilbert MC, Su LK, Vogelstein B, Bryan TM, Levy DB, Smith KJ, Preisinger AC, Hedge P, McKechnie D et al (1991) Identification of FAP locus genes from chromosome 5q21. Science 253(5020):661–665

    Article  CAS  PubMed  Google Scholar 

  43. Wallace MR, Marchuk DA, Andersen LB, Letcher R, Odeh HM, Saulino AM, Fountain JW, Brereton A, Nicholson J, Mitchell AL et al (1990) Type 1 neurofibromatosis gene: identification of a large transcript disrupted in three NF1 patients. Science 249(4965):181–186

    Article  CAS  PubMed  Google Scholar 

  44. Tomczak K, Czerwińska P, Wiznerowicz M (2015) The Cancer Genome Atlas (TCGA): an immeasurable source of knowledge. Contemp Oncol 2015(19):A68–A77

    Google Scholar 

  45. Chang K, Creighton CJ, Davis C, Donehower L, Drummond J, Wheeler D, Ally A, Balasundaram M, Birol I, Butterfield YS et al (2013) The Cancer Genome Atlas Pan-Cancer analysis project. Nat Genet 45(10):1113–1120

    Article  CAS  Google Scholar 

  46. Zhang J, Baran J, Cros A, Guberman JM, Haider S, Hsu J, Liang Y, Rivkin E, Wang J, Whitty B, Wong-Erasmus M, Yao L, Kasprzyk A (2011) International Cancer Genome Consortium Data Portal—a one-stop shop for cancer genomics data. Database (Oxford) 2011:bar026. https://doi.org/10.1093/database/bar026

    PubMed  PubMed Central  Google Scholar 

  47. Whitehead I, Kirk H, Kay R (1995) Expression cloning of oncogenes by retroviral transfer of cDNA libraries. Mol Cell Biol 15(2):704–710

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Wan D, Gong Y, Qin W, Zhang P, Li J, Wei L, Zhou X, Li H, Qiu X, Zhong F, He L, Yu J, Yao G, Jiang H, Qian L, Yu Y, Shu H, Chen X, Xu H, Guo M, Pan Z, Chen Y, Ge C, Yang S, Gu J (2004) Large-scale cDNA transfection screening for genes related to cancer development and progression. Proc Natl Acad Sci U S A 101(44):15724–15729. https://doi.org/10.1073/pnas.0404089101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Schlabach MR, Luo J, Solimini NL, Hu G, Xu Q, Li MZ, Zhao Z, Smogorzewska A, Sowa ME, Ang XL, Westbrook TF, Liang AC, Chang K, Hackett JA, Harper JW, Hannon GJ, Elledge SJ (2008) Cancer proliferation gene discovery through functional genomics. Science 319(5863):620–624. https://doi.org/10.1126/science.1149200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Laufer C, Fischer B, Billmann M, Huber W, Boutros M (2013) Mapping genetic interactions in human cancer cells with RNAi and multiparametric phenotyping. Nat Methods 10(5):427–431. https://doi.org/10.1038/nmeth.2436

    Article  CAS  PubMed  Google Scholar 

  51. Silva JM, Marran K, Parker JS, Silva J, Golding M, Schlabach MR, Elledge SJ, Hannon GJ, Chang K (2008) Profiling essential genes in human mammary cells by multiplex RNAi screening. Science 319(5863):617–620. https://doi.org/10.1126/science.1149185

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Prahallad A, Sun C, Huang S, Di Nicolantonio F, Salazar R, Zecchin D, Beijersbergen RL, Bardelli A, Bernards R (2012) Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR. Nature 483(7387):100–103. https://doi.org/10.1038/nature10868

    Article  CAS  PubMed  Google Scholar 

  53. Koike-Yusa H, Li Y, Tan EP, Velasco-Herrera Mdel C, Yusa K (2014) Genome-wide recessive genetic screening in mammalian cells with a lentiviral CRISPR-guide RNA library. Nat Biotechnol 32(3):267–273. https://doi.org/10.1038/nbt.2800

    Article  CAS  PubMed  Google Scholar 

  54. Hart T, Chandrashekhar M, Aregger M, Steinhart Z, Brown KR, MacLeod G, Mis M, Zimmermann M, Fradet-Turcotte A, Sun S, Mero P, Dirks P, Sidhu S, Roth FP, Rissland OS, Durocher D, Angers S, Moffat J (2015) High-resolution CRISPR screens reveal fitness genes and genotype-specific cancer liabilities. Cell 163(6):1515–1526. https://doi.org/10.1016/j.cell.2015.11.015

    Article  CAS  PubMed  Google Scholar 

  55. Gilbert LA, Horlbeck MA, Adamson B, Villalta JE, Chen Y, Whitehead EH, Guimaraes C, Panning B, Ploegh HL, Bassik MC, Qi LS, Kampmann M, Weissman JS (2014) Genome-scale CRISPR-mediated control of gene repression and activation. Cell 159(3):647–661. https://doi.org/10.1016/j.cell.2014.09.029

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Ivics Z, Hackett PB, Plasterk RH, Izsvak Z (1997) Molecular reconstruction of Sleeping Beauty, a Tc1-like transposon from fish, and its transposition in human cells. Cell 91(4):501–510

    Article  CAS  PubMed  Google Scholar 

  57. de Jong J, Akhtar W, Badhai J, Rust AG, Rad R, Hilkens J, Berns A, van Lohuizen M, Wessels LF, de Ridder J (2014) Chromatin landscapes of retroviral and transposon integration profiles. PLoS Genet 10(4):e1004250. https://doi.org/10.1371/journal.pgen.1004250

    Article  PubMed  PubMed Central  Google Scholar 

  58. Yoshida J, Akagi K, Misawa R, Kokubu C, Takeda J, Horie K (2017) Chromatin states shape insertion profiles of the piggyBac, Tol2 and Sleeping Beauty transposons and murine leukemia virus. Sci Rep 7:43613. https://doi.org/10.1038/srep43613

    Article  PubMed  PubMed Central  Google Scholar 

  59. Acevedo-Arozena A, Wells S, Potter P, Kelly M, Cox RD, Brown SD (2008) ENU mutagenesis, a way forward to understand gene function. Annu Rev Genomics Hum Genet 9:49–69

    Article  CAS  PubMed  Google Scholar 

  60. Cordes SP (2005) N-ethyl-N-nitrosourea mutagenesis: boarding the mouse mutant express. Microbiol Mol Biol Rev 69(3):426–439. https://doi.org/10.1128/MMBR.69.3.426-439.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Moser AR, Pitot HC, Dove WF (1990) A dominant mutation that predisposes to multiple intestinal neoplasia in the mouse. Science 247(4940):322–324

    Article  CAS  PubMed  Google Scholar 

  62. Fenske TS, McMahon C, Edwin D, Jarvis JC, Cheverud JM, Minn M, Mathews V, Bogue MA, Province MA, McLeod HL, Graubert TA (2006) Identification of candidate alkylator-induced cancer susceptibility genes by whole genome scanning in mice. Cancer Res 66(10):5029–5038. https://doi.org/10.1158/0008-5472.CAN-05-3404

    Article  CAS  PubMed  Google Scholar 

  63. Uren AG, Kool J, Berns A, van Lohuizen M (2005) Retroviral insertional mutagenesis: past, present and future. Oncogene 24(52):7656–7672

    Article  CAS  PubMed  Google Scholar 

  64. Kawakami K, Largaespada DA, Ivics Z (2017) Transposons as tools for functional genomics in vertebrate models. Trends Genet 33:784–801. https://doi.org/10.1016/j.tig.2017.07.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Starr TK, Largaespada DA (2005) Cancer gene discovery using the sleeping beauty transposon. Cell Cycle 4(12):1744–1748

    Article  CAS  PubMed  Google Scholar 

  66. Abbott KL, Nyre ET, Abrahante J, Ho YY, Isaksson Vogel R, Starr TK (2015) The Candidate Cancer Gene Database: a database of cancer driver genes from forward genetic screens in mice. Nucleic Acids Res 43(Database issue):D844–D848. https://doi.org/10.1093/nar/gku770

    Article  CAS  PubMed  Google Scholar 

  67. Newberg JY, Mann KM, Mann MB, Jenkins NA, Copeland NG (2017) SBCDDB: Sleeping Beauty Cancer Driver Database for gene discovery in mouse models of human cancers. Nucleic Acids Res 46:D1011–D1017. https://doi.org/10.1093/nar/gkx956

    Article  CAS  PubMed Central  Google Scholar 

  68. Starr TK, Scott PM, Marsh BM, Zhao L, Than BL, O’Sullivan MG, Sarver AL, Dupuy AJ, Largaespada DA, Cormier RT (2011) A Sleeping Beauty transposon-mediated screen identifies murine susceptibility genes for adenomatous polyposis coli (Apc)-dependent intestinal tumorigenesis. Proc Natl Acad Sci U S A 108(14):5765–5770. https://doi.org/10.1073/pnas.1018012108

    Article  PubMed  PubMed Central  Google Scholar 

  69. March HN, Rust AG, Wright NA, Ten Hoeve J, de Ridder J, Eldridge M, van der Weyden L, Berns A, Gadiot J, Uren A, Kemp R, Arends MJ, Wessels LF, Winton DJ, Adams DJ (2011) Insertional mutagenesis identifies multiple networks of cooperating genes driving intestinal tumorigenesis. Nat Genet 43:1202–1209. https://doi.org/10.1038/ng.990

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Takeda H, Wei Z, Koso H, Rust AG, Yew CC, Mann MB, Ward JM, Adams DJ, Copeland NG, Jenkins NA (2015) Transposon mutagenesis identifies genes and evolutionary forces driving gastrointestinal tract tumor progression. Nat Genet 47:142–150. https://doi.org/10.1038/ng.3175

    Article  CAS  PubMed  Google Scholar 

  71. Montero-Conde C, Leandro-Garcia LJ, Chen X, Oler G, Ruiz-Llorente S, Ryder M, Landa I, Sanchez-Vega F, La K, Ghossein RA, Bajorin DF, Knauf JA, Riordan JD, Dupuy AJ, Fagin JA (2017) Transposon mutagenesis identifies chromatin modifiers cooperating with Ras in thyroid tumorigenesis and detects ATXN7 as a cancer gene. Proc Natl Acad Sci U S A 114:E4951–E4960. https://doi.org/10.1073/pnas.1702723114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. de la Rosa J, Weber J, Rad R, Bradley A, Cadinanos J (2017) Disentangling PTEN-cooperating tumor suppressor gene networks in cancer. Mol Cell Oncol 4(4):e1325550. https://doi.org/10.1080/23723556.2017.1325550

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Dorr C, Janik C, Weg M, Been RA, Bader J, Kang R, Ng B, Foran L, Landman SR, O’Sullivan MG, Steinbach M, Sarver AL, Silverstein KA, Largaespada DA, Starr TK (2015) Transposon mutagenesis screen identifies potential lung cancer drivers and CUL3 as a tumor suppressor. Mol Cancer Res 13(8):1238–1247. https://doi.org/10.1158/1541-7786.MCR-14-0674-T

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Timothy K. Starr .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Clark, C.R., DuRose, W., Starr, T.K. (2019). Cancer Gene Discovery: Past to Present. In: Starr, T. (eds) Cancer Driver Genes. Methods in Molecular Biology, vol 1907. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8967-6_1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-8967-6_1

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-8966-9

  • Online ISBN: 978-1-4939-8967-6

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics