1932

Abstract

The basic catalog of DNA-based alterations that contribute to the onset and progression of cancer has been largely elucidated due to the results obtained from the combination of massively parallel sequencing and computational analysis methods applied to thousands of cancer samples. These combined approaches have provided novel and surprising insights into the myriad ways that DNA-level disruptions lead to activation and inactivation of cellular pathways, thereby altering the carefully controlled growth and division of normal cells and rendering them cancerous. This review presents genomic insights gained from these large-scale studies and highlights how this new knowledge will be translated in the future into improved clinical care and monitoring of cancer patients.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-cancerbio-050216-122035
2018-03-04
2024-04-15
Loading full text...

Full text loading...

/deliver/fulltext/cancerbio/2/1/annurev-cancerbio-050216-122035.html?itemId=/content/journals/10.1146/annurev-cancerbio-050216-122035&mimeType=html&fmt=ahah

Literature Cited

  1. Amary MF, Bacsi K, Maggiani F, Damato S, Halai D. et al. 2011. IDH1 and IDH2 mutations are frequent events in central chondrosarcoma and central and periosteal chondromas but not in other mesenchymal tumours. J. Pathol. 224:3334–43 [Google Scholar]
  2. Azad NS, El-Khoueiry A, Yin J, Oberg AL, Flynn P. et al. 2017. Combination epigenetic therapy in metastatic colorectal cancer (mCRC) with subcutaneous 5-azacitidine and entinostat: a phase 2 consortium/Stand Up 2 Cancer study. Oncotarget 8:35326–38 [Google Scholar]
  3. Bardelli A, Parsons DW, Silliman N, Ptak J, Szabo S. et al. 2003. Mutational analysis of the tyrosine kinome in colorectal cancers. Science 300:5621949 [Google Scholar]
  4. Bettegowda C, Sausen M, Leary RJ, Kinde I, Wang Y. et al. 2014. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci. Transl. Med. 6:224224ra24 [Google Scholar]
  5. Borger DR, Tanabe KK, Fan KC, Lopez HU, Fantin VR. et al. 2012. Frequent mutation of isocitrate dehydrogenase (IDH)1 and IDH2 in cholangiocarcinoma identified through broad-based tumor genotyping. Oncologist 17:172–79 [Google Scholar]
  6. Cancer Genome Atlas Res. Netw. 2011. Integrated genomic analyses of ovarian carcinoma. Nature 474:7353609–15 [Google Scholar]
  7. Cancer Genome Atlas Res. Netw. 2012. Comprehensive molecular portraits of human breast tumours. Nature 490:741861–70 [Google Scholar]
  8. Cancer Genome Atlas Res. Netw. 2013.a Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N. Engl. J. Med. 368:222059–74 [Google Scholar]
  9. Cancer Genome Atlas Res. Netw. 2013.b Integrated genomic characterization of endometrial carcinoma. Nature 497:744767–73 [Google Scholar]
  10. Chaisson MJP, Huddleston J, Dennis MY, Sudmant PH, Malig M. et al. 2015.a Resolving the complexity of the human genome using single-molecule sequencing. Nature 517:7536608–11 [Google Scholar]
  11. Chaisson MJP, Wilson RK, Eichler EE. 2015.b Genetic variation and the de novo assembly of human genomes. Nat. Rev. Genet. 16:11627–40 [Google Scholar]
  12. Deb S, Xu H, Tuynman J, George J, Yan Y. et al. 2014. RAD21 cohesin overexpression is a prognostic and predictive marker exacerbating poor prognosis in KRAS mutant colorectal carcinomas. Br. J. Cancer 110:61606–13 [Google Scholar]
  13. Ding L, Ellis MJ, Li S, Larson DE, Chen K. et al. 2010. Genome remodelling in a basal-like breast cancer metastasis and xenograft. Nature 464:7291999–1005 [Google Scholar]
  14. Ding L, Ley TJ, Larson DE, Miller CA, Koboldt DC. et al. 2012. Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing. Nature 481:7382506–10 [Google Scholar]
  15. Druker BJ, Tamura S, Buchdunger E, Ohno S, Segal GM. et al. 1996. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr–Abl positive cells. Nat. Med. 2:5561–66 [Google Scholar]
  16. Ellis MJ, Ding L, Shen D, Luo J, Suman VJ. et al. 2012. Whole-genome analysis informs breast cancer response to aromatase inhibition. Nature 486:7403353–60 [Google Scholar]
  17. Ewalt M, Galili NG, Mumtaz M, Churchill M, Rivera S. et al. 2011. DNMT3a mutations in high-risk myelodysplastic syndrome parallel those found in acute myeloid leukemia. Blood Cancer J 1:3e9 [Google Scholar]
  18. Furney SJ, Pedersen M, Gentien D, Dumont AG, Rapinat A. et al. 2013. SF3B1 mutations are associated with alternative splicing in uveal melanoma. Cancer Discov 3:101122–29 [Google Scholar]
  19. Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D. et al. 2012. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N. Engl. J. Med. 366:10883–92 [Google Scholar]
  20. Golomb HM, Rowley JD. 1981. Significance of cytogenetic abnormalities in acute leukemias. Hum. Pathol. 12:6515–22 [Google Scholar]
  21. Hanahan D, Weinberg RA. 2011. Hallmarks of cancer: the next generation. Cell 144:5646–74 [Google Scholar]
  22. Hillier LD, Lennon G, Becker M, Bonaldo MF, Chiapelli B. et al. 1996. Generation and analysis of 280,000 human expressed sequence tags. Genome Res 6:9807–28 [Google Scholar]
  23. Hou JP, Ma J. 2014. DawnRank: discovering personalized driver genes in cancer. Genome Med 6:756 [Google Scholar]
  24. Huang ME, Ye YC, Chen SR, Chai JR, Lu JX. et al. 1988. Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood 72:2567–72 [Google Scholar]
  25. Int. Hum. Genome Seq. Consort. 2004. Finishing the euchromatic sequence of the human genome. Nature 431:7011931–45 [Google Scholar]
  26. Jackman SD, Vandervalk BP, Mohamadi H, Chu J, Yeo S. et al. 2017. ABySS 2.0: resource-efficient assembly of large genomes using a Bloom filter. Genome Res 27:768–77 [Google Scholar]
  27. Jones S, Anagnostou V, Lytle K, Parpart-Li S, Nesselbush M. et al. 2015. Personalized genomic analyses for cancer mutation discovery and interpretation. Sci. Transl. Med. 7:283283ra53 [Google Scholar]
  28. Juric D, Castel P, Griffith M, Griffith OL, Won HH. et al. 2015. Convergent loss of PTEN leads to clinical resistance to a PI(3)Kα inhibitor. Nature 518:7538240–44 [Google Scholar]
  29. Kandoth C, McLellan MD, Vandin F, Ye K, Niu B. et al. 2013. Mutational landscape and significance across 12 major cancer types. Nature 502:333–39 [Google Scholar]
  30. Kar SA, Jankowska A, Makishima H, Visconte V, Jerez A. et al. 2013. Spliceosomal gene mutations are frequent events in the diverse mutational spectrum of chronic myelomonocytic leukemia but largely absent in juvenile myelomonocytic leukemia. Haematologica 98:1107–13 [Google Scholar]
  31. Kohno T, Nakaoku T, Tsuta K, Tsuchihara K, Matsumoto S. et al. 2015. Beyond ALK-RET, ROS1 and other oncogene fusions in lung cancer. Transl. Lung Cancer Res. 4:156–64 [Google Scholar]
  32. Kon A, Shih L-Y, Minamino M, Sanada M, Shiraishi Y. et al. 2013. Recurrent mutations in multiple components of the cohesin complex in myeloid neoplasms. Nat. Genet. 45:101232–37 [Google Scholar]
  33. Larson RA, Kondo K, Vardiman JW, Butler AE, Golomb HM, Rowley JD. 1984. Evidence for a 15;17 translocation in every patient with acute promyelocytic leukemia. Am. J. Med. 76:5827–41 [Google Scholar]
  34. Le Beau MM, Westbrook CA, Diaz MO, Rowley JD, Oren M. 1985. Translocation of the p53 gene in t(15;17) in acute promyelocytic leukaemia. Nature 316:6031826–28 [Google Scholar]
  35. Leiserson MDM, Vandin F, Wu H-T, Dobson JR, Eldridge JV. et al. 2015. Pan-cancer network analysis identifies combinations of rare somatic mutations across pathways and protein complexes. Nat. Genet. 47:2106–14 [Google Scholar]
  36. Ley TJ, Ding L, Walter MJ, McLellan MD, Lamprecht T. et al. 2010. DNMT3A mutations in acute myeloid leukemia. N. Engl. J. Med. 363:252424–33 [Google Scholar]
  37. Ley TJ, Mardis ER, Ding L, Fulton B, McLellan MD. et al. 2008. DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome. Nature 456:721866–72 [Google Scholar]
  38. Ley TJ, Minx PJ, Walter MJ, Ries RE, Sun H. et al. 2003. A pilot study of high-throughput, sequence-based mutational profiling of primary human acute myeloid leukemia cell genomes. PNAS 100:2414275–80 [Google Scholar]
  39. Li H, Durbin R. 2009. Fast and accurate short read alignment with Burrows–Wheeler transform. Bioinformatics 25:141754–60 [Google Scholar]
  40. Li H, Handsaker B, Wysoker A, Fennell T, Ruan J. et al. 2009. The Sequence Alignment/Map format and SAMtools. Bioinformatics 25:162078–79 [Google Scholar]
  41. Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA. et al. 2004. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N. Engl. J. Med. 350:212129–39 [Google Scholar]
  42. Maguire SL, Leonidou A, Wai P, Marchiò C, Ng CK. et al. 2015. SF3B1 mutations constitute a novel therapeutic target in breast cancer. J. Pathol. 235:4571–80 [Google Scholar]
  43. Mardis ER. 2011. A decade's perspective on DNA sequencing technology. Nature 470:7333198–203 [Google Scholar]
  44. Mardis ER. 2013. Next-generation sequencing platforms. Annu. Rev. Anal. Chem. 6:287–303 [Google Scholar]
  45. Mardis ER. 2017. DNA sequencing technologies: 2006–2016. Nat. Protoc. 12:2213–18 [Google Scholar]
  46. Mardis ER, Ding L, Dooling DJ, Larson DE, McLellan MD. et al. 2009. Recurring mutations found by sequencing an acute myeloid leukemia genome. N. Engl. J. Med. 361:111058–66 [Google Scholar]
  47. Mazumdar C, Shen Y, Xavy S, Zhao F, Reinisch A. et al. 2015. Leukemia-associated cohesin mutants dominantly enforce stem cell programs and impair human hematopoietic progenitor differentiation. Cell Stem Cell 17:6675–88 [Google Scholar]
  48. Mullenders J, Aranda-Orgilles B, Lhoumaud P, Keller M, Pae J. et al. 2015. Cohesin loss alters adult hematopoietic stem cell homeostasis, leading to myeloproliferative neoplasms. J. Exp. Med. 212:111833–50 [Google Scholar]
  49. Murugaesu N, Wilson GA, Birkbak NJ, Watkins TBK, McGranahan N. et al. 2015. Tracking the genomic evolution of esophageal adenocarcinoma through neoadjuvant chemotherapy. Cancer Discov 5:8821–31 [Google Scholar]
  50. Paez JG, Jänne PA, Lee JC, Tracy S, Greulich H. et al. 2004. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304:56761497–500 [Google Scholar]
  51. Pao W, Miller VA, Politi KA, Riely GJ, Somwar R. et al. 2005. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLOS Med 2:3e73 [Google Scholar]
  52. Pao W, Miller VA, Zakowski M, Doherty J, Politi K. et al. 2004. EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinib. PNAS 101:3613306–11 [Google Scholar]
  53. Parsons DW, Jones S, Zhang X, Lin JC-H, Leary RJ. et al. 2008. An integrated genomic analysis of human glioblastoma multiforme. Science 321:58971807–12 [Google Scholar]
  54. Polymeropoulos MH, Xiao H, Glodek A, Gorski M, Adams MD. et al. 1992. Chromosomal assignment of 46 brain cDNAs. Genomics 12:3492–96 [Google Scholar]
  55. Rossi D, Bruscaggin A, Spina V, Rasi S, Khiabanian H. et al. 2011. Mutations of the SF3B1 splicing factor in chronic lymphocytic leukemia: association with progression and fludarabine-refractoriness. Blood 118:266904–8 [Google Scholar]
  56. Rowley JD. 1973. Letter: a new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature 243:5405290–93 [Google Scholar]
  57. Rowley JD, Golomb HM, Dougherty C. 1977.a 15/17 translocation, a consistent chromosomal change in acute promyelocytic leukaemia. Lancet 1:8010549–50 [Google Scholar]
  58. Rowley JD, Golomb HM, Vardiman J, Fukuhara S, Dougherty C, Potter D. 1977.b Further evidence for a non-random chromosomal abnormality in acute promyelocytic leukemia. Int. J. Cancer 20:6869–72 [Google Scholar]
  59. Saha S, Sparks AB, Rago C, Akmaev V, Wang CJ. et al. 2002. Using the transcriptome to annotate the genome. Nat. Biotechnol. 20:5508–12 [Google Scholar]
  60. Shah SP, Morin RD, Khattra J, Prentice L, Pugh T. et al. 2009. Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution. Nature 461:7265809–13 [Google Scholar]
  61. Sheer D, Sheppard DM, le Beau M, Rowley JD, San Roman C, Solomon E. 1985. Localization of the oncogene c-erbA1 immediately proximal to the acute promyelocytic leukaemia breakpoint on chromosome 17. Ann. Hum. Genet. 49:Pt. 3167–71 [Google Scholar]
  62. Sjöblom T, Jones S, Wood LD, Parsons DW, Lin J. et al. 2006. The consensus coding sequences of human breast and colorectal cancers. Science 314:5797268–74 [Google Scholar]
  63. Stracquadanio G, Wang X, Wallace MD, Grawenda AM, Zhang P. et al. 2016. The importance of p53 pathway genetics in inherited and somatic cancer genomes. Nat. Rev. Cancer 16:4251–65 [Google Scholar]
  64. Susswein LR, Marshall ML, Nusbaum R, Vogel Postula KJ, Weissman SM. et al. 2016. Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing. Genet. Med. 18:8823–32 [Google Scholar]
  65. Tie J, Wang Y, Tomasetti C, Li L, Springer S. et al. 2016. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer. Sci. Transl. Med. 8:346346ra92 [Google Scholar]
  66. Vecchione L, Gambino V, Raaijmakers J, Schlicker A, Fumagalli A. et al. 2016. A vulnerability of a subset of colon cancers with potential clinical utility. Cell 165:2317–30 [Google Scholar]
  67. Viny AD, Ott CJ, Spitzer B, Rivas M, Meydan C. et al. 2015. Dose-dependent role of the cohesin complex in normal and malignant hematopoiesis. J. Exp. Med. 212:111819–32 [Google Scholar]
  68. Walter MJ, Ding L, Shen D, Shao J, Grillot M. et al. 2011. Recurrent DNMT3A mutations in patients with myelodysplastic syndromes. Leukemia 25:71153–58 [Google Scholar]
  69. Wang L, Lawrence MS, Wan Y, Stojanov P, Sougnez C. et al. 2011. SF3B1 and other novel cancer genes in chronic lymphocytic leukemia. N. Engl. J. Med. 365:262497–506 [Google Scholar]
  70. Wang T-L, Rago C, Silliman N, Ptak J, Markowitz S. et al. 2002. Prevalence of somatic alterations in the colorectal cancer cell genome. PNAS 99:53076–80 [Google Scholar]
  71. Ward PS, Patel J, Wise DR, Abdel-Wahab O, Bennett BD. et al. 2010. The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting α-ketoglutarate to 2-hydroxyglutarate. Cancer Cell 17:3225–34 [Google Scholar]
  72. Weisenfeld NI, Kumar V, Shah P, Church DM, Jaffe DB. 2017. Direct determination of diploid genome sequences. Genome Res 27:757–67 [Google Scholar]
  73. Wood LD, Parsons DW, Jones S, Lin J, Sjöblom T. et al. 2007. The genomic landscapes of human breast and colorectal cancers. Science 318:58531108–13 [Google Scholar]
  74. Xiang Z, Zhao Y, Mitaksov V, Fremont DH, Kasai Y. et al. 2008. Identification of somatic JAK1 mutations in patients with acute myeloid leukemia. Blood 111:94809–12 [Google Scholar]
  75. Yoshida K, Sanada M, Shiraishi Y, Nowak D, Nagata Y. et al. 2011. Frequent pathway mutations of splicing machinery in myelodysplasia. Nature 478:736764–69 [Google Scholar]
  76. Zhang J, Walsh MF, Wu G, Edmonson MN, Gruber TA. et al. 2015. Germline mutations in predisposition genes in pediatric cancer. N. Engl. J. Med. 373:242336–46 [Google Scholar]
  77. Zhang L, Zhou W, Velculescu VE, Kern SE, Hruban RH. et al. 1997. Gene expression profiles in normal and cancer cells. Science 276:53161268–72 [Google Scholar]
/content/journals/10.1146/annurev-cancerbio-050216-122035
Loading
/content/journals/10.1146/annurev-cancerbio-050216-122035
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error