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Recent Advances in Cancer Genomics and Cancer-Associated Genes Discovery

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An Omics Perspective on Cancer Research

Abstract

Human cancer is a personalized disease characterized by complex molecular genetic abnormalities unique to individual patients. Studying cancer genome has defined much of the molecular pathogenesis of neoplasia we have understood so far and has supported the view that cancer is a genetic disease caused by sequential accumulation of genetic alterations. Recent advances in genome-wide technologies have provided unprecedented tools to reveal the genomic landscape of cancer in great detail, and thus have offered new opportunity in deciphering the specific genomic changes participated in tumor initiation and progression. Here, we review these emergent array- or sequencing-based technologies and provide examples of how they can be applied in discovering molecular genetic changes in cancer and in facilitating mining of important cancer genes. From a clinical perspective, it appears a daunting challenge in translating those molecular genetic findings from cancer cells to cancer patients. Therefore, we will also briefly discuss the potential problems in translational cancer genomic research and propose the possible solutions.

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References

  • Baselga J (2006) Targeting tyrosine kinases in cancer: the second wave. Science 312:1175–1178

    Article  CAS  PubMed  Google Scholar 

  • Bentires-Alj M, Gil SG, Chan R et al (2006) A role for the scaffolding adapter GAB2 in breast cancer. Nat Med 12:114–121

    Article  CAS  PubMed  Google Scholar 

  • Bosma PT, van Eert SJ, Jaspers NG et al (2003) Functional cloning of drug resistance genes from retroviral cDNA libraries. Biochem Biophys Res Commun 309:605–611

    Article  CAS  PubMed  Google Scholar 

  • Brown LA, Kalloger SE, Miller MA et al (2008) Amplification of 11q13 in ovarian carcinoma. Genes Chromosomes Cancer 47:481–489

    Article  CAS  PubMed  Google Scholar 

  • Campbell PJ, Stephens PJ, Pleasance ED et al (2008) Identification of somatically acquired rearrangements in cancer using genome-wide massively parallel paired-end sequencing. Nat Genet 40:722–729

    Article  CAS  PubMed  Google Scholar 

  • Carter NP (2007) Methods and strategies for analyzing copy number variation using DNA microarrays. Nat Genet 39:S16–21

    Article  CAS  PubMed  Google Scholar 

  • Chi KR (2008) The year of sequencing. Nat Methods 5:11–14

    Article  CAS  PubMed  Google Scholar 

  • Choi JH, Sheu J, Guan B et al (2009) Functional analysis of 11q13.5 amplicon identifies Rsf-1 (HBXAP) as a gene involved in paclitaxel resistance in ovarian cancer. Cancer Res 69:1407–1415

    Article  CAS  PubMed  Google Scholar 

  • Dalton WS, Friend SH (2006) Cancer biomarkers – an invitation to the table. Science 312:1165–1168

    Article  CAS  PubMed  Google Scholar 

  • Dobbe E, Gurney K, Kiekow S et al (2008) Gene-expression assays: new tools to individualize treatment of early-stage breast cancer. Am J Health Syst Pharm 65:23–28

    Article  CAS  PubMed  Google Scholar 

  • Dohm JC, Lottaz C, Borodina T et al (2008) Substantial biases in ultra-short read data sets from high-throughput DNA sequencing. Nucleic Acids Res 36:e105

    Article  PubMed  Google Scholar 

  • Duan J, Wainwright MS, Comeron JM et al (2003) Synonymous mutations in the human dopamine receptor D2 (DRD2) affect mRNA stability and synthesis of the receptor. Hum Mol Genet 12:205–216

    Article  CAS  PubMed  Google Scholar 

  • Easton DF, Pooley KA, Dunning AM et al (2007) Genome-wide association study identifies novel breast cancer susceptibility loci. Nature 447:1087–1093

    Article  CAS  PubMed  Google Scholar 

  • Eeles RA, Kote-Jarai Z, Giles GG et al (2008) Multiple newly identified loci associated with prostate cancer susceptibility. Nat Genet 40:316–321

    Article  CAS  PubMed  Google Scholar 

  • Erlich Y, Mitra PP, DelaBastide M et al (2008) Alta-Cyclic: a self-optimizing base caller for next-generation sequencing. Nat Methods 5:679–682

    Article  CAS  PubMed  Google Scholar 

  • Feuk L, Carson AR, Scherer SW (2006) Structural variation in the human genome. Nat Rev Genet 7:85–97

    Article  CAS  PubMed  Google Scholar 

  • Greenman C, Stephens P, Smith R et al (2007) Patterns of somatic mutation in human cancer genomes. Nature 446:153–158

    Article  CAS  PubMed  Google Scholar 

  • Gudmundsson J, Sulem P, Rafnar T et al (2008) Common sequence variants on 2p15 and Xp11.22 confer susceptibility to prostate cancer. Nat Genet 40:281–283

    Article  CAS  PubMed  Google Scholar 

  • Haber DA, Settleman J (2007) Cancer: drivers and passengers. Nature 446:145–146

    Article  CAS  PubMed  Google Scholar 

  • Heim S, Mitelman F (2008) Molecular screening for new fusion genes in cancer. Nat Genet 40:685–686

    Article  CAS  PubMed  Google Scholar 

  • Hillier LW, Marth GT, Quinlan AR et al (2008) Whole-genome sequencing and variant discovery in C. elegans. Nat Methods 5:183–188

    Article  CAS  PubMed  Google Scholar 

  • Ishkanian AS, Malloff CA, Watson SK et al (2004) A tiling resolution DNA microarray with complete coverage of the human genome. Nat Genet 36:299–303

    Article  CAS  PubMed  Google Scholar 

  • Jones S, Zhang X, Parsons DW et al (2008) Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 1164368 321:1801–1806

    Google Scholar 

  • Kallioniemi A, Kallioniemi OP, Sudar D et al (1992) Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors. Science 258:818–821

    Article  CAS  PubMed  Google Scholar 

  • Kimchi-Sarfaty C, Oh JM, Kim IW et al (2007) A “silent” polymorphism in the MDR1 gene changes substrate specificity. Science 315:525–528

    Article  CAS  PubMed  Google Scholar 

  • Kinzler KW, Vogelstein B (2002) The genetic basis of human cancer, 2nd edn. McGraw-Hill, Toronto

    Google Scholar 

  • Kittler R, Pelletier L, Heninger AK et al (2007) Genome-scale RNAi profiling of cell division in human tissue culture cells. Nat Cell Biol 9:1401–1412

    Article  CAS  PubMed  Google Scholar 

  • Korbel JO, Urban AE, Affourtit JP et al (2007) Paired-end mapping reveals extensive structural variation in the human genome. Science 318:420–426

    Article  CAS  PubMed  Google Scholar 

  • Levy S, Sutton G, Ng PC et al (2007) The diploid genome sequence of an individual human. PLoS Biol 5:e254

    Article  PubMed  Google Scholar 

  • Ley TJ, Mardis ER, Ding L et al (2008) DNA sequencing of a cytogenetically normal acute myeloid leukemia genome. Nature 456:66–72

    Article  CAS  PubMed  Google Scholar 

  • Lucito R, Healy J, Alexander J et al (2003) Representational oligonucleotide microarray analysis: a high-resolution method to detect genome copy number variation. Genome Res 13:2291–2305

    Article  CAS  PubMed  Google Scholar 

  • Mao X, Young BD, Lu YJ (2007) The application of single nucleotide polymorphism microarrays in cancer research. Curr Genomics 8:219–228

    Article  CAS  PubMed  Google Scholar 

  • Matsumura H, Reich S, Ito A et al (2003) Gene expression analysis of plant host–pathogen interactions by SuperSAGE. Proc Natl Acad Sci USA 100:15718–15723

    Article  CAS  PubMed  Google Scholar 

  • Merlo LM, Pepper JW, Reid BJ et al (2006) Cancer as an evolutionary and ecological process. Nat Rev Cancer 6:924–935

    Article  CAS  PubMed  Google Scholar 

  • Mitelman F, Johansson B, Mertens F (2007) The impact of translocations and gene fusions on cancer causation. Nat Rev Cancer 7:233–245

    Article  CAS  PubMed  Google Scholar 

  • Mukherji M, Bell R, Supekova L et al (2006) Genome-wide functional analysis of human cell-cycle regulators. Proc Natl Acad Sci USA 103:14819–14824

    Article  CAS  PubMed  Google Scholar 

  • Nackley AG, Shabalina SA, Tchivileva IE et al (2006) Human catechol-O-methyltransferase haplotypes modulate protein expression by altering mRNA secondary structure. Science 314:1930–1933

    Article  CAS  PubMed  Google Scholar 

  • Nakayama K, Nakayama N, Jinawath N et al (2007) Amplicon profiles in ovarian serous carcinomas. Int J Cancer 120:2613–2617

    Article  CAS  PubMed  Google Scholar 

  • Ng P, Tan JJ, Ooi HS et al (2006) Multiplex sequencing of paired-end ditags (MS-PET): a strategy for the ultra-high-throughput analysis of transcriptomes and genomes. Nucleic Acids Res 34:e84

    Article  PubMed  Google Scholar 

  • Ng P, Wei CL, Sung WK et al (2005) Gene identification signature (GIS) analysis for transcriptome characterization and genome annotation. Nat Methods 2:105–111

    Article  CAS  PubMed  Google Scholar 

  • Paik S, Shak S, Tang G et al (2004) A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 351:2817–2826

    Article  CAS  PubMed  Google Scholar 

  • Parsons DW, Jones S, Zhang X et al (2008) An Integrated Genomic Analysis of Human Glioblastoma Multiforme. Science 1164382

    Google Scholar 

  • Pinkel D, Albertson DG (2005) Array comparative genomic hybridization and its applications in cancer. Nat Genet 37:S11–S17

    Article  CAS  PubMed  Google Scholar 

  • Prat J, Ribe A, Gallardo A (2005) Hereditary ovarian cancer. Hum Pathol 36:861–870

    Article  CAS  PubMed  Google Scholar 

  • Ruan Y, Ooi HS, Choo SW et al (2007) Fusion transcripts and transcribed retrotransposed loci discovered through comprehensive transcriptome analysis using Paired-End diTags (PETs). Genome Res 17:828–838

    Article  CAS  PubMed  Google Scholar 

  • Rusk N, Kiermer V (2008) Primer: Sequencing–the next generation. Nat Methods 5:15

    Article  CAS  PubMed  Google Scholar 

  • Schlabach MR, Luo J, Solimini NL et al (2008) Cancer proliferation gene discovery through functional genomics. Science 319:620–624

    Article  CAS  PubMed  Google Scholar 

  • Schraml P, Schwerdtfeger G, Burkhalter F et al (2003) Combined array comparative genomic hybridization and tissue microarray analysis suggest PAK1 at 11q13.5–q14 as a critical oncogene target in ovarian carcinoma. Am J Pathol 163:985–992

    CAS  PubMed  Google Scholar 

  • Schuster SC (2008) Next-generation sequencing transforms today’s biology. Nat Methods 5:16–18

    Article  CAS  PubMed  Google Scholar 

  • Schwab M (1998) Amplification of oncogenes in human cancer cells. Bioessays 20:473–479

    Article  CAS  PubMed  Google Scholar 

  • Shih Ie M, Sheu JJ, Santillan A et al (2005) Amplification of a chromatin remodeling gene, Rsf-1/ HBXAP, in ovarian carcinoma. Proc Natl Acad Sci USA 102:14004–14009

    Article  PubMed  Google Scholar 

  • Shih IM, Wang TL (2005) Apply innovative technologies to explore cancer genome. Curr Opin Oncol 17:33–38

    Article  CAS  PubMed  Google Scholar 

  • Sjoblom T, Jones S, Wood LD et al (2006) The consensus coding sequences of human breast and colorectal cancers. Science 314:268–274

    Article  PubMed  Google Scholar 

  • Soda M, Choi YL, Enomoto M et al (2007) Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 448:561–566

    Article  CAS  PubMed  Google Scholar 

  • Thomas G, Jacobs KB, Yeager M et al (2008) Multiple loci identified in a genome-wide association study of prostate cancer. Nat Genet 40:310–315

    Article  CAS  PubMed  Google Scholar 

  • Tuzun E, Sharp AJ, Bailey JA et al (2005) Fine-scale structural variation of the human genome. Nat Genet 37:727–732

    Article  CAS  PubMed  Google Scholar 

  • van de Vijver MJ, He YD, van’t Veer LJ et al (2002) A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med 347:1999–2009

    Google Scholar 

  • Volik S, Zhao S, Chin K et al (2003) End-sequence profiling: sequence-based analysis of aberrant genomes. Proc Natl Acad Sci USA 100:7696–7701

    Article  PubMed  Google Scholar 

  • Wang J, Wang W, Li R et al (2008) The diploid genome sequence of an Asian individual. Nature 456:60–65

    Article  CAS  PubMed  Google Scholar 

  • Wang K, Li M, Hadley D et al (2007) PennCNV: an integrated hidden Markov model designed for high-resolution copy number variation detection in whole-genome SNP genotyping data. Genome Res 17:1665–1674

    Article  CAS  PubMed  Google Scholar 

  • Wang TL, Diaz LA Jr, Romans K et al (2004) Digital karyotyping identifies thymidylate synthase amplification as a mechanism of resistance to 5-fluorouracil in metastatic colorectal cancer patients. Proc Natl Acad Sci USA 101:3089–3094

    Article  CAS  PubMed  Google Scholar 

  • Wang TL, Maierhofer C, Speicher MR et al (2002) Digital karyotyping. Proc Natl Acad Sci USA 99:16156–16161

    Article  CAS  PubMed  Google Scholar 

  • Ward RL, Hawkins NJ (2001) Checking the scoreboard: the impact of cancer genetics on clinical practice. Intern Med J 31:249–253

    Article  CAS  PubMed  Google Scholar 

  • Weir BA, Woo MS, Getz G et al (2007) Characterizing the cancer genome in lung adenocarcinoma. Nature 450:893–898

    Article  CAS  PubMed  Google Scholar 

  • Wheeler DA, Srinivasan M, Egholm M et al (2008) The complete genome of an individual by massively parallel DNA sequencing. Nature 452:872–876

    Article  CAS  PubMed  Google Scholar 

  • Witt AE, Hines LM, Collins NL et al (2006) Functional proteomics approach to investigate the biological activities of cDNAs implicated in breast cancer. J Proteome Res 5:599–610

    Article  CAS  PubMed  Google Scholar 

  • Wold B, Myers RM (2008) Sequence census methods for functional genomics. Nat Methods 5:19–21

    Article  CAS  PubMed  Google Scholar 

  • Wood LD, Parsons DW, Jones S et al (2007) The genomic landscapes of human breast and colorectal cancers. Science 318:1108–1113

    Article  CAS  PubMed  Google Scholar 

  • Ylstra B, van den Ijssel P, Carvalho B et al (2006) BAC to the future! or oligonucleotides: a perspective for micro array comparative genomic hybridization (array CGH). Nucleic Acids Res 34:445–450

    Article  CAS  PubMed  Google Scholar 

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Acknowledgement

Part of this study was supported by an NIH/NCI grant (RO1 CA129080).

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Correspondence to Ie-Ming Shih .

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Guan, B., Wang, TL., Shih, IM. (2010). Recent Advances in Cancer Genomics and Cancer-Associated Genes Discovery. In: Cho, W. (eds) An Omics Perspective on Cancer Research. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-2675-0_2

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