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Cancer Genomics and Precision Medicine: A Way Toward Early Diagnosis and Effective Cancer Treatment

  • Ritika Tiwari
  • Bushra AteeqEmail author
Chapter

Abstract

Since the first draft of the Human Genome Project was completed in April 2003, biomedical researchers have been mining and extrapolating genomic data toward the goal of improving human health and realizing medical benefits. The promise of “personalized oncomedicine,” the matching of therapeutics to appropriate molecular targets in individual cancer patients, lies in the convergence of cancer researchers, computational biologist, and clinicians to identify the driving mutations involved in tumor progression and metastasis and pursue appropriate therapies. The virtual concept of “cancer genome” in the development of uncontrolled cell growth was conceived as early as late nineteenth and early twentieth century by Theodor Boveri (Boveri 2008). Boveri hypothesized that malignant tumors could be the result of a certain abnormal condition of the chromosomes arising from multipolar mitosis. Several decades later the discovery of the Philadelphia chromosome as the genetic driver of chronic myeloid leukemia (CML) provided the experimental evidence for Boveri’s hypothesis (Nowell and Hungerford 1961).

Keywords

Chronic Myeloid Leukemia Transcriptome Sequencing Solitary Fibrous Tumor Polycomb Repressive Complex Fusion Transcript 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

We thank Jyoti Athanikar for critically reading the manuscript. B.A. is an Intermediate Fellow of the Wellcome Trust-DBT India Alliance [IA/I(S)/12/2/500635 to BA] and a Young Investigator of the DST-FAST Track scheme.

Competing Interests

No competing interests to be disclosed.

Dr. Bushra Ateeq

Dr. Bushra Ateeq is an Assistant Professor at Department of Biological Sciences and Bioengineering (BSBE), IIT, Kanpur, India. The primary research focus of Dr. Bushra’s laboratory is to understand the complex molecular events involved in prostate and breast cancer, identify early diagnostic markers and valuable therapeutic targets. Her lab focuses on experimental evaluation of the functional relevance of the genetic rearrangements, copy number changes, and somatic alterations identified by genomic approaches, using molecular and cellular approaches.

References

  1. Amaral PP, Dinger ME, Mercer TR, Mattick JS. The eukaryotic genome as an RNA machine. Science. 2008;319:1787–9.CrossRefPubMedGoogle Scholar
  2. Arrowsmith CH, Bountra C, Fish PV, Lee K, Schapira M. Epigenetic protein families: a new frontier for drug discovery. Nat Rev Drug Discov. 2012;11:384–400.CrossRefPubMedGoogle Scholar
  3. Ateeq B, Unterberger A, Szyf M, Rabbani SA. Pharmacological inhibition of DNA methylation induces proinvasive and prometastatic genes in vitro and in vivo. Neoplasia. 2008;10:266–78.CrossRefPubMedPubMedCentralGoogle Scholar
  4. Baylin SB, Jones PA. A decade of exploring the cancer epigenome—biological and translational implications. Nat Rev Cancer. 2011;11:726–34.CrossRefPubMedPubMedCentralGoogle Scholar
  5. Boveri T. Concerning the origin of malignant tumours by Theodor Boveri. Translated and annotated by Harris H. J Cell Sci. 2008;121 Suppl 1:1–84.Google Scholar
  6. Cao Q, et al. Repression of E-cadherin by the polycomb group protein EZH2 in cancer. Oncogene. 2008;27:7274–84.CrossRefPubMedPubMedCentralGoogle Scholar
  7. Cazier JB, et al. Whole-genome sequencing of bladder cancers reveals somatic CDKN1A mutations and clinicopathological associations with mutation burden. Nat Commun. 2014;5:3756.CrossRefPubMedPubMedCentralGoogle Scholar
  8. Chinnaiyan AM, Palanisamy N. Chromosomal aberrations in solid tumors. Prog Mol Biol Transl Sci. 2010;95:55–94.CrossRefPubMedGoogle Scholar
  9. Cokus SJ, et al. Shotgun bisulphite sequencing of the Arabidopsis genome reveals DNA methylation patterning. Nature. 2008;452:215–9.CrossRefPubMedPubMedCentralGoogle Scholar
  10. Crea F, et al. Identification of a long non-coding RNA as a novel biomarker and potential therapeutic target for metastatic prostate cancer. Oncotarget. 2014;5:764–74.CrossRefPubMedPubMedCentralGoogle Scholar
  11. Druker BJ, et al. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med. 1996;2:561–6.CrossRefPubMedGoogle Scholar
  12. Eswaran J, et al. RNA sequencing of cancer reveals novel splicing alterations. Sci Rep. 2013;3:1689.CrossRefPubMedPubMedCentralGoogle Scholar
  13. Fong PC, et al. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med. 2009;361:123–34.CrossRefPubMedGoogle Scholar
  14. Forbes SA, et al. COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer. Nucleic Acids Res. 2011;39:D945–50.CrossRefPubMedGoogle Scholar
  15. Frommer M, et al. A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands. Proc Natl Acad Sci USA. 1992;89:1827–31.CrossRefPubMedPubMedCentralGoogle Scholar
  16. Grasso CS, et al. The mutational landscape of lethal castration-resistant prostate cancer. Nature. 2012;487:239–43.CrossRefPubMedPubMedCentralGoogle Scholar
  17. Groffen J, Stephenson JR, Heisterkamp N, de Klein A, Bartram CR, Grosveld G. Philadelphia chromosomal breakpoints are clustered within a limited region, bcr, on chromosome 22. Cell. 1984;36:93–9.CrossRefPubMedGoogle Scholar
  18. Johnson GL, Lapadat R. Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science. 2002;298:1911–2.CrossRefPubMedGoogle Scholar
  19. Kalyana-Sundaram S, et al. Expressed pseudogenes in the transcriptional landscape of human cancers. Cell. 2012;149:1622–34.CrossRefPubMedPubMedCentralGoogle Scholar
  20. Khan SN, et al. Multiple mechanisms deregulate EZH2 and histone H3 lysine 27 epigenetic changes in myeloid malignancies. Leukemia. 2013;27:1301–9.CrossRefPubMedGoogle Scholar
  21. Kim JH, et al. Deep sequencing reveals distinct patterns of DNA methylation in prostate cancer. Genome Res. 2011;21:1028–41.CrossRefPubMedPubMedCentralGoogle Scholar
  22. Kogo R, et al. Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers. Cancer Res. 2011;71:6320–6.CrossRefPubMedGoogle Scholar
  23. Kouzarides T. Chromatin modifications and their function. Cell. 2007;128:693–705.CrossRefPubMedGoogle Scholar
  24. Li X, Gonzalez ME, Toy K, Filzen T, Merajver SD, Kleer CG. Targeted overexpression of EZH2 in the mammary gland disrupts ductal morphogenesis and causes epithelial hyperplasia. Am J Pathol. 2009;175:1246–54.CrossRefPubMedPubMedCentralGoogle Scholar
  25. Li H, Ruan J, Durbin R. Mapping short DNA sequencing reads and calling variants using mapping quality scores. Genome Res. 2008;18:1851–8.CrossRefPubMedPubMedCentralGoogle Scholar
  26. Lugo TG, Pendergast AM, Muller AJ, Witte ON. Tyrosine kinase activity and transformation potency of bcr-abl oncogene products. Science. 1990;247:1079–82.CrossRefPubMedGoogle Scholar
  27. Lynch TJ, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004;350:2129–39.CrossRefPubMedGoogle Scholar
  28. Maher CA, et al. Transcriptome sequencing to detect gene fusions in cancer. Nature. 2009;458:97–101.CrossRefPubMedPubMedCentralGoogle Scholar
  29. Mardis ER, Wilson RK. Cancer genome sequencing: a review. Hum Mol Genet. 2009;18:R163–8.CrossRefPubMedPubMedCentralGoogle Scholar
  30. Marioni JC, Mason CE, Mane SM, Stephens M, Gilad Y. RNA-seq: an assessment of technical reproducibility and comparison with gene expression arrays. Genome Res. 2008;18:1509–17.CrossRefPubMedPubMedCentralGoogle Scholar
  31. Martelli MP, et al. EML4-ALK rearrangement in non-small cell lung cancer and non-tumor lung tissues. Am J Pathol. 2009;174:661–70.CrossRefPubMedPubMedCentralGoogle Scholar
  32. Meyerson M, Gabriel S, Getz G. Advances in understanding cancer genomes through second-generation sequencing. Nat Rev Genet. 2010;11:685–96.CrossRefPubMedGoogle Scholar
  33. Mitelman F. Recurrent chromosome aberrations in cancer. Mutat Res. 2000;462:247–53.CrossRefPubMedGoogle Scholar
  34. Mitelman F, Johansson B, Mertens F. The impact of translocations and gene fusions on cancer causation. Nat Rev Cancer. 2007;7:233–45.CrossRefPubMedGoogle Scholar
  35. Morin RD, et al. Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin. Nat Genet. 2010;42:181–5.CrossRefPubMedPubMedCentralGoogle Scholar
  36. Morin RD, et al. Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma. Nature. 2011;476:298–303.CrossRefPubMedPubMedCentralGoogle Scholar
  37. Natrajan R, et al. Characterization of the genomic features and expressed fusion genes in micropapillary carcinomas of the breast. J Pathol. 2014;232:553–65.CrossRefPubMedPubMedCentralGoogle Scholar
  38. Nowell PC, Hungerford DA. Chromosome studies in human leukemia. II. Chronic granulocytic leukemia. J Natl Cancer Inst. 1961;27:1013–35.PubMedGoogle Scholar
  39. Palanisamy N, et al. Rearrangements of the RAF kinase pathway in prostate cancer, gastric cancer and melanoma. Nat Med. 2010;16:793–8.CrossRefPubMedPubMedCentralGoogle Scholar
  40. Pao W, Miller V, Zakowski M, Doherty J, Politi K, Sarkaria I, et al. EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci USA. 2004;101:13306–11.CrossRefPubMedPubMedCentralGoogle Scholar
  41. Pong RC, et al. Epigenetic regulation of coxsackie and adenovirus receptor (CAR) gene promoter in urogenital cancer cells. Cancer Res. 2003;63:8680–6.PubMedGoogle Scholar
  42. Robertson D. Genentech’s anticancer Mab expected by November. Nat Biotechnol. 1998;16:615.CrossRefPubMedGoogle Scholar
  43. Robinson DR, et al. Identification of recurrent NAB2-STAT6 gene fusions in solitary fibrous tumor by integrative sequencing. Nat Genet. 2013a;45:180–5.CrossRefPubMedPubMedCentralGoogle Scholar
  44. Robinson DR, et al. Activating ESR1 mutations in hormone-resistant metastatic breast cancer. Nat Genet. 2013b;45:1446–51.CrossRefPubMedPubMedCentralGoogle Scholar
  45. Rowley JD. Ph1-positive leukaemia, including chronic myelogenous leukaemia. Clin Haematol. 1980;9:55–86.PubMedGoogle Scholar
  46. Schechter AL, et al. The neu oncogene: an erb-B-related gene encoding a 185,000-Mr tumour antigen. Nature. 1984;312:513–6.CrossRefPubMedGoogle Scholar
  47. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235:177–82.CrossRefPubMedGoogle Scholar
  48. Stephens PJ, et al. Complex landscapes of somatic rearrangement in human breast cancer genomes. Nature. 2009;462:1005–10.CrossRefPubMedPubMedCentralGoogle Scholar
  49. Stransky N, Cerami E, Schalm S, Kim JL, Lengauer C. The landscape of kinase fusions in cancer. Nat Commun. 2014;5:4846.CrossRefPubMedPubMedCentralGoogle Scholar
  50. Stratton MR, Campbell PJ, Futreal PA. The cancer genome. Nature. 2009;458:719–24.CrossRefPubMedPubMedCentralGoogle Scholar
  51. Sultan M, et al. A global view of gene activity and alternative splicing by deep sequencing of the human transcriptome. Science. 2008;321:956–60.CrossRefPubMedGoogle Scholar
  52. Szyf M. Therapeutic implications of DNA methylation. Future Oncol. 2005;1:125–35.CrossRefPubMedGoogle Scholar
  53. Tan M, et al. Identification of 67 histone marks and histone lysine crotonylation as a new type of histone modification. Cell. 2011;146:1016–28.CrossRefPubMedPubMedCentralGoogle Scholar
  54. Tomlins SA, et al. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science. 2005;310:644–8.CrossRefPubMedGoogle Scholar
  55. van Haaften G, et al. Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer. Nat Genet. 2009;41:521–3.CrossRefPubMedPubMedCentralGoogle Scholar
  56. Varambally S, et al. Genomic loss of microRNA-101 leads to overexpression of histone methyltransferase EZH2 in cancer. Science. 2008;322:1695–9.CrossRefPubMedPubMedCentralGoogle Scholar
  57. Wang KC, Chang HY. Molecular mechanisms of long noncoding RNAs. Mol Cell. 2011;43:904–14.CrossRefPubMedPubMedCentralGoogle Scholar
  58. Wu H, et al. Genome-wide analysis of 5-hydroxymethylcytosine distribution reveals its dual function in transcriptional regulation in mouse embryonic stem cells. Genes Dev. 2011;25:679–84.CrossRefPubMedPubMedCentralGoogle Scholar
  59. Yoshida K, et al. The landscape of somatic mutations in down syndrome-related myeloid disorders. Nat Genet. 2013;45:1293–9.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2017

Authors and Affiliations

  1. 1.Department of Biological Sciences and BioengineeringIndian Institute of TechnologyKanpurIndia

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