Abstract
According to mainstream thinking in the past three decades, cancer is a disease of the genome. That is, cancer evolves from benign to malignant lesions by accumulating a series of genetic mutations over time. This model was initially developed for colorectal cancers based on mutations in the APC gene (Fearon and Vogelstein 1990) and a few other recurring genomic mutations that have been observed in colorectal cancers. To drive the genetic basis of this and other cancers, extensive collaborative efforts have been established to sequence the genomes of numerous cancer types, predominantly solid tumors. This undertaking has led to the public availability of thousands of cancer genomes and the identification of myriad genomic mutations, including single-point mutations, copy-number changes and genomic rearrangements. Analyses of the sequenced genomes have observed that a cancer genome may harbor tens to a few tens of thousands of mutations across different cancer types. One somewhat surprising observation has been that cancer genomes tend to have a high degree of heterogeneity in terms of their mutation patterns among tissue samples of the same cancer type, even among different cells in the same cancer tissue (Xu et al. 2012). From this, an obvious question is: Which of the observed mutations contribute to the initiation and development of a sporadic cancer, and how? Or, from another perspective, are any of these mutations responsible for tumor initiation, progression and metastasis?
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Barbieri CE, Baca SC, Lawrence MS et al. (2012) Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer. Nature genetics 44: 685–689
Becchetti A (2011) Ion channels and transporters in cancer. 1. Ion channels and cell proliferation in cancer. American journal of physiology Cell physiology 301: C255–265
Bozic I, Antal T, Ohtsuki H et al. (2010) Accumulation of driver and passenger mutations during tumor progression. Proceedings of the National Academy of Sciences of the United States of America 107: 18545–18550
Coustan-Smith E, Mullighan CG, Onciu M et al. (2009) Early T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemia. Lancet Oncol 10: 147–156
Croft D, O’Kelly G, Wu G et al. (2011) Reactome: a database of reactions, pathways and biological processes. Nucleic acids research 39: D691–697
Cui J, Yin Y, Ma Q et al. (2014) Towards Understanding the Genomic Alterations in Human Gastric Cancer. In review.
de Caestecker MP, Piek E, Roberts AB (2000) Role of transforming growth factor-beta signaling in cancer. Journal of the National Cancer Institute 92: 1388–1402
Deininger M, Buchdunger E, Druker BJ (2005) The development of imatinib as a therapeutic agent for chronic myeloid leukemia. Blood 105: 2640–2653
Fearnhead NS, Britton MP, Bodmer WF (2001) The ABC of APC. Human molecular genetics 10: 721–733
Fearon ER, Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61: 759–767
Ferreira VP, Pangburn MK, Cortes C (2010) Complement control protein factor H: the good, the bad, and the inadequate. Molecular immunology 47: 2187–2197
Fletcher JI, Haber M, Henderson MJ et al. (2010) ABC transporters in cancer: more than just drug efflux pumps. Nature reviews Cancer 10: 147–156
Genetics-Home-Reference (2014) AMER1.
Guan B, Wang TL, Shih Ie M (2011) ARID1A, a factor that promotes formation of SWI/SNF-mediated chromatin remodeling, is a tumor suppressor in gynecologic cancers. Cancer research 71: 6718–6727
Herst PM, Berridge MV (2006) Plasma membrane electron transport: a new target for cancer drug development. Current molecular medicine 6: 895–904
Hirayama A, Kami K, Sugimoto M et al. (2009) Quantitative metabolome profiling of colon and stomach cancer microenvironment by capillary electrophoresis time-of-flight mass spectrometry. Cancer research 69: 4918–4925
Hochhaus A (2006) Chronic myelogenous leukemia (CML): resistance to tyrosine kinase inhibitors. Annals of Oncology 17: x274–x279
Jordan K, Schaeffer V, Fischer K et al. (2006) Notch signaling through Tramtrack bypasses the mitosis promoting activity of the JNK pathway in the mitotic-to-endocycle transition of Drosophila follicle cells. BMC Developmental Biology 6: 1–12
Kahane N, Ribes V, Kicheva A et al. (2013) The transition from differentiation to growth during dermomyotome-derived myogenesis depends on temporally restricted hedgehog signaling. Development 140: 1740–1750
Kaiser J (2010) UPDATED: A Skeptic Questions Cancer Genome Projects. Available at: http://news.sciencemag.org/2010/04/updated-skeptic-questions-cancer-genome-projects.
Kent J, Wheatley SC, Andrews JE et al. (1996) A male-specific role for SOX9 in vertebrate sex determination. Development 122: 2813–2822
Kinzler KW, Vogelstein B (1996) Lessons from hereditary colorectal cancer. Cell 87: 159–170
Lakin ND, Jackson SP (1999) Regulation of p53 in response to DNA damage. Oncogene 18: 7644–7655
Lander ES, Linton LM, Birren B et al. (2001) Initial sequencing and analysis of the human genome. Nature 409: 860–921
Li C, Bapat B, Alman BA (1998) Adenomatous polyposis coli gene mutation alters proliferation through its beta-catenin-regulatory function in aggressive fibromatosis (desmoid tumor). The American journal of pathology 153: 709–714
Litman T, Moeller S, Echwald SM et al. (2008) Novel human micrornas associated with cancer. Google Patents,
Liu P, Morrison C, Wang L et al. (2012) Identification of somatic mutations in non-small cell lung carcinomas using whole-exome sequencing. Carcinogenesis 33: 1270–1276
Lu C, Ward PS, Kapoor GS et al. (2012) IDH mutation impairs histone demethylation and results in a block to cell differentiation. Nature 483: 474–478
Medema JP (2013) Cancer stem cells: the challenges ahead. Nature cell biology 15: 338–344
Meza R, Jeon J, Moolgavkar SH et al. (2008) Age-specific incidence of cancer: Phases, transitions, and biological implications. Proceedings of the National Academy of Sciences of the United States of America 105: 16284–16289
Murat CB, Braga PB, Fortes MA et al. (2012) Mutation and genomic amplification of the PIK3CA proto-oncogene in pituitary adenomas. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas/Sociedade Brasileira de Biofisica [et al] 45: 851–855
Nagarajan N, Bertrand D, Hillmer AM et al. (2012) Whole-genome reconstruction and mutational signatures in gastric cancer. Genome Biol 13: R115
Nikolaev SI, Sotiriou SK, Pateras IS et al. (2012) A single-nucleotide substitution mutator phenotype revealed by exome sequencing of human colon adenomas. Cancer research 72: 6279–6289
Nishimura D (2001) BioCarta. Biotech Software & Internet Report 2:
Ogata H, Goto S, Sato K et al. (1999) KEGG: Kyoto Encyclopedia of Genes and Genomes. Nucleic acids research 27: 29–34
Pleasance ED, Cheetham RK, Stephens PJ et al. (2010a) A comprehensive catalogue of somatic mutations from a human cancer genome. Nature 463: 191–196
Pleasance ED, Stephens PJ, O’Meara S et al. (2010b) A small-cell lung cancer genome with complex signatures of tobacco exposure. Nature 463: 184–190
Serizawa M, Koh Y, Kenmotsu H et al. (2013) Multiplexed mutational profiling of Japanese lung adenocarcinoma patients for personalized cancer therapy. Cancer research 73: supplement 1
Shi Y, Hu Z, Wu C et al. (2011) A genome-wide association study identifies new susceptibility loci for non-cardia gastric cancer at 3q13.31 and 5p13.1. Nature genetics 43: 1215–1218
Szakacs G, Paterson JK, Ludwig JA et al. (2006) Targeting multidrug resistance in cancer. Nature reviews Drug discovery 5: 219–234
The-Cancer-Genome-Atlas (2012a) Comprehensive genomic characterization of squamous cell lung cancers. Nature 489: 519–525
The-Cancer-Genome-Atlas (2012b) Comprehensive molecular characterization of human colon and rectal cancer. Nature 487: 330–337
Thomas J, Wang LH, Clark RE et al. (2004) Active transport of imatinib into and out of cells: implications for drug resistance. Blood 104: 3739–3745
Vaux DL, Weissman IL (1993) Neither macromolecular synthesis nor myc is required for cell death via the mechanism that can be controlled by Bcl-2. Molecular and cellular biology 13: 7000–7005
Venter JC, Adams MD, Myers EW et al. (2001) The sequence of the human genome. Science 291: 1304–1351
Vogelstein B, Kinzler KW (2004) Cancer genes and the pathways they control. Nature medicine 10: 789–799
Vogelstein B, Papadopoulos N, Velculescu VE et al. (2013) Cancer genome landscapes. Science 339: 1546–1558
Wang K, Kan J, Yuen ST et al. (2011) Exome sequencing identifies frequent mutation of ARID1A in molecular subtypes of gastric cancer. Nature genetics 43: 1219–1223
Weinstein RS (1976) Changes in plasma membrane structure associated with malignant transformation in human urinary bladder epithelium. Cancer research 36: 2518–2524
Wells RG (2008) The role of matrix stiffness in regulating cell behavior. Hepatology 47: 1394–1400
Xu X, Hou Y, Yin X et al. (2012) Single-cell exome sequencing reveals single-nucleotide mutation characteristics of a kidney tumor. Cell 148: 886–895
Zhang J, Ding L, Holmfeldt L et al. (2012) The genetic basis of early T-cell precursor acute lymphoblastic leukaemia. Nature 481: 157–163
Zilfou JT, Lowe SW (2009) Tumor suppressive functions of p53. Cold Spring Harbor perspectives in biology 1: a001883
Author information
Authors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer Science+Business Media New York
About this chapter
Cite this chapter
Xu, Y., Cui, J., Puett, D. (2014). Understanding Cancer at the Genomic Level. In: Cancer Bioinformatics. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1381-7_4
Download citation
DOI: https://doi.org/10.1007/978-1-4939-1381-7_4
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4939-1380-0
Online ISBN: 978-1-4939-1381-7
eBook Packages: Computer ScienceComputer Science (R0)