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Detection of Alternatively Spliced or Processed RNAs in Cancer Using Oligonucleotide Microarray

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RNA and Cancer

Part of the book series: Cancer Treatment and Research ((CTAR,volume 158))

Abstract

Deregulation of gene expression plays a pivotal role in tumorigenesis, so the ability to detect RNA alterations is of great value in cancer diagnosis and management. DNA microarrays have been used to measure changes in mRNA or microRNA level, but less often the change of RNA isoforms. Here we appraise the utilization of microarray in detecting alternatively processed RNAs, which have alternative splice forms, retained introns, or altered 3′ untranslated regions. We cover the methodology and focus on cancer studies. Recent development in parallel or deep sequencing used in transcriptome analysis is also discussed.

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References

  1. Clark TA, Sugnet CW, Ares M Jr (2002) Genome-wide analysis of mRNA processing in yeast using splicing-specific microarrays. Science 296:907–910

    Article  PubMed  CAS  Google Scholar 

  2. Johnson JM, Castle J, Garrett-Engele P et al (2003) Genome-wide survey of human alternative pre-mRNA splicing with exon junction microarrays. Science 302:2141–2144

    Article  PubMed  CAS  Google Scholar 

  3. Pan Q, Shai O, Misquitta C et al (2004) Revealing global regulatory features of mammalian alternative splicing using a quantitative microarray platform. Mol Cell 16:929–941

    Article  PubMed  CAS  Google Scholar 

  4. Fehlbaum P, Guihal C, Bracco L et al (2005) A microarray configuration to quantify expression levels and relative abundance of splice variants. Nucleic Acids Res 33:e47

    Article  PubMed  Google Scholar 

  5. Srinivasan K, Shiue L, Hayes JD et al (2005) Detection and measurement of alternative splicing using splicing-sensitive microarrays. Methods 37:345–359

    Article  PubMed  CAS  Google Scholar 

  6. Castle J, Garrett-Engele P, Armour CD et al (2003) Optimization of oligonucleotide arrays and RNA amplification protocols for analysis of transcript structure and alternative splicing. Genome Biol 4:R66

    Article  PubMed  Google Scholar 

  7. Relogio A, Ben-Dov C, Baum M et al (2005) Alternative splicing microarrays reveal functional expression of neuron-specific regulators in Hodgkin lymphoma cells. J Biol Chem 280:4779–4784

    Article  PubMed  CAS  Google Scholar 

  8. Li C, Kato M, Shiue L et al (2006) Cell type and culture condition-dependent alternative splicing in human breast cancer cells revealed by splicing-sensitive microarrays. Cancer Res 66:1990–1999

    Article  PubMed  CAS  Google Scholar 

  9. Pio R, Blanco D, Pajares MJ et al (2010) Development of a novel splice array platform and its application in the identification of alternative splice variants in lung cancer. BMC genomics 11:352

    Article  PubMed  Google Scholar 

  10. Zhou W, Calciano MA, Jordan H et al (2009) High resolution analysis of the human transcriptome: detection of extensive alternative splicing independent of transcriptional activity. BMC Genet 10:63

    Article  PubMed  Google Scholar 

  11. Srinivasan S, Bingham JL, Johnson D (2009) The ABCs of human alternative splicing: a review of ATP-binding cassette transporter splicing. Curr Opin Drug Discov Devel 12:149–158

    PubMed  CAS  Google Scholar 

  12. Yeakley JM, Fan JB, Doucet D et al (2002) Profiling alternative splicing on fiber-optic arrays. Nat Biotechnol 20:353–358

    Article  PubMed  CAS  Google Scholar 

  13. Fan JB, Yeakley JM, Bibikova M et al (2004) A versatile assay for high-throughput gene expression profiling on universal array matrices. Genome Res 14:878–885

    Article  PubMed  CAS  Google Scholar 

  14. Zhang C, Li HR, Fan JB et al (2006) Profiling alternatively spliced mRNA isoforms for prostate cancer classification. BMC Bioinformatics 7:202

    Article  PubMed  Google Scholar 

  15. Li HR, Wang-Rodriguez J, Nair TM et al (2006) Two-dimensional transcriptome profiling: identification of messenger RNA isoform signatures in prostate cancer from archived paraffin-embedded cancer specimens. Cancer Res 66:4079–4088

    Article  PubMed  CAS  Google Scholar 

  16. Fan JB, Gunderson KL, Bibikova M et al (2006) Illumina universal bead arrays. Methods Enzymol 410:57–73

    Article  PubMed  CAS  Google Scholar 

  17. Gardina PJ, Clark TA, Shimada B et al (2006) Alternative splicing and differential gene expression in colon cancer detected by a whole genome exon array. BMC Genomics 7:325

    Article  PubMed  Google Scholar 

  18. Robinson MD, Speed TP (2007) A comparison of Affymetrix gene expression arrays. BMC Bioinformatics 8:449

    Article  PubMed  Google Scholar 

  19. Abdueva D, Wing MR, Schaub B, Triche TJ (2007) Experimental comparison and evaluation of the Affymetrix exon and U133Plus2 Gene Chip arrays. PLoS ONE 2:e913

    Article  PubMed  Google Scholar 

  20. Okoniewski MJ, Hey Y, Pepper SD, Miller CJ (2007) High correspondence between Affymetrix exon and standard expression arrays. Biotechniques 42:181–185

    Article  PubMed  CAS  Google Scholar 

  21. Xing Y, Kapur K, Wong WH (2006) Probe selection and expression index computation of Affymetrix Exon Arrays. PLoS ONE 1:e88

    Article  PubMed  Google Scholar 

  22. Kapur K, Xing Y, Ouyang Z, Wong WH (2007) Exon arrays provide accurate assessments of gene expression. Genome Biol 8:R82

    Article  PubMed  Google Scholar 

  23. Okumura M, Kondo S, Ogata M et al (2005) Candidates for tumor-specific alternative splicing. Biochem Biophys Res Commun 334:23–29

    Article  PubMed  CAS  Google Scholar 

  24. Xu Q, Lee C (2003) Discovery of novel splice forms and functional analysis of cancer-specific alternative splicing in human expressed sequences. Nucleic Acids Res 31:5635–5643

    Article  PubMed  CAS  Google Scholar 

  25. Thorsen K, Sorensen KD, Brems-Eskildsen AS et al (2008) Alternative splicing in colon, bladder, and prostate cancer identified by exon array analysis. Mol Cell Proteomics 7:1214–1224

    Article  PubMed  CAS  Google Scholar 

  26. French PJ, Peeters J, Horsman S et al (2007) Identification of differentially regulated splice variants and novel exons in glial brain tumors using exon expression arrays. Cancer Res 67:5635–5642

    Article  PubMed  CAS  Google Scholar 

  27. Cheung HC, Baggerly KA, Tsavachidis S et al (2008) Global analysis of aberrant pre-mRNA splicing in glioblastoma using exon expression arrays. BMC Genomics 9:216

    Article  PubMed  Google Scholar 

  28. Hallegger M, Llorian M, Smith CW (2010) Alternative splicing: global insights. The FEBS J 277:856–866

    Article  CAS  Google Scholar 

  29. Lapuk A, Marr H, Jakkula L et al (2010) Exon-level microarray analyses identify alternative splicing programs in breast cancer. Mol Cancer Res 8:961–974

    Article  PubMed  CAS  Google Scholar 

  30. Subbaram S, Kuentzel M, Frank D et al (2010) Determination of alternate splicing events using the Affymetrix Exon 1.0 ST arrays. Method Mol Biol 632:63–72

    Article  CAS  Google Scholar 

  31. Yeo GW, Xu X, Liang TY et al (2007) Alternative splicing events identified in human embryonic stem cells and neural progenitors. PLoS Comput Biol 3:1951–1967

    Article  PubMed  CAS  Google Scholar 

  32. Xing Y, Stoilov P, Kapur K et al (2008) MADS: a new and improved method for analysis of differential alternative splicing by exon-tiling microarrays. RNA 14:1470–1479

    Article  PubMed  CAS  Google Scholar 

  33. Boutz PL, Stoilov P, Li Q et al (2007) A post-transcriptional regulatory switch in polypyrimidine tract-binding proteins reprograms alternative splicing in developing neurons. Genes Dev 21:1636–1652

    Article  PubMed  CAS  Google Scholar 

  34. Mockler TC, Chan S, Sundaresan A et al (2005) Applications of DNA tiling arrays for whole-genome analysis. Genomics 85:1–15

    Article  PubMed  CAS  Google Scholar 

  35. Johnson JM, Edwards S, Shoemaker D, Schadt EE (2005) Dark matter in the genome: evidence of widespread transcription detected by microarray tiling experiments. Trends Genet 21:93–102

    Article  PubMed  CAS  Google Scholar 

  36. Yazaki J, Gregory BD, Ecker JR (2007) Mapping the genome landscape using tiling array technology. Curr Opin Plant Biol 10:534–542

    Article  PubMed  CAS  Google Scholar 

  37. Kapranov P, Cawley SE, Drenkow J et al (2002) Large-scale transcriptional activity in chromosomes 21 and 22. Science 296:916–919

    Article  PubMed  CAS  Google Scholar 

  38. Kampa D, Cheng J, Kapranov P et al (2004) Novel RNAs identified from an in-depth analysis of the transcriptome of human chromosomes 21 and 22. Genome Res 14:331–342

    Article  PubMed  CAS  Google Scholar 

  39. Bertone P, Stolc V, Royce TE et al (2004) Global identification of human transcribed sequences with genome tiling arrays. Science 306:2242–2246

    Article  PubMed  CAS  Google Scholar 

  40. Cheng J, Kapranov P, Drenkow J et al (2005) Transcriptional maps of 10 human chromosomes at 5-nucleotide resolution. Science 308:1149–1154

    Article  PubMed  CAS  Google Scholar 

  41. Okazaki Y, Furuno M, Kasukawa T et al (2002) Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs. Nature 420:563–573

    Article  PubMed  Google Scholar 

  42. Stolc V, Gauhar Z, Mason C et al (2004) A gene expression map for the euchromatic genome of Drosophila melanogaster. Science 306:655–660

    Article  PubMed  CAS  Google Scholar 

  43. Yamada K, Lim J, Dale JM et al (2003) Empirical analysis of transcriptional activity in the Arabidopsis genome. Science 302:842–846

    Article  PubMed  CAS  Google Scholar 

  44. Birney E, Stamatoyannopoulos JA, Dutta A et al (2007) Identification and analysis of functional elements in 1 % of the human genome by the ENCODE pilot project. Nature 447:799–816

    Article  PubMed  CAS  Google Scholar 

  45. Denoeud F, Kapranov P, Ucla C et al (2007) Prominent use of distal 5’ transcription start sites and discovery of a large number of additional exons in ENCODE regions. Genome Res 17:746–759

    Article  PubMed  CAS  Google Scholar 

  46. Le Hir H, Charlet-Berguerand N, de Franciscis V, Thermes C (2002) 5’-End RET splicing: absence of variants in normal tissues and intron retention in pheochromocytomas. Oncology 63:84–91

    Article  PubMed  Google Scholar 

  47. Lee MP, Feinberg AP (1997) Aberrant splicing but not mutations of TSG101 in human breast cancer. Cancer Res 57:3131–3134

    PubMed  CAS  Google Scholar 

  48. Kim E, Goren A, Ast G (2008) Insights into the connection between cancer and alternative splicing. Trends Genet 24:7–10

    Article  PubMed  CAS  Google Scholar 

  49. Juneau K, Palm C, Miranda M, Davis RW (2007) High-density yeast-tiling array reveals previously undiscovered introns and extensive regulation of meiotic splicing. Proc Natl Acad Sci USA 104:1522–1527

    Article  PubMed  CAS  Google Scholar 

  50. Sayani S, Janis M, Lee CY, Toesca I, Chanfreau GF (2008) Widespread impact of nonsense-mediated mRNA decay on the yeast intronome. Mol Cell 31:360–370

    Article  PubMed  CAS  Google Scholar 

  51. Gencheva M, Lin TY, Wu X et al (2010) Nuclear retention of unspliced pre-mRNAs by mutant DHX16/hPRP2, a spliceosomal DEAH-box protein. J Biol Chem 285:35624–35632

    Article  PubMed  CAS  Google Scholar 

  52. Sakharkar MK, Perumal BS, Sakharkar KR, Kangueane P (2005) An analysis on gene architecture in human and mouse genomes. In Silico Biol 5:347–365

    PubMed  CAS  Google Scholar 

  53. Yang L, Lin G, Wu X, Yen Y, Lin R-J Novel RNAs overexpressed in breast tumors as revealed by genomic tiling microarray. (In Preparation)

    Google Scholar 

  54. Gudlaugsdottir S, Boswell DR, Wood GR, Ma J (2007) Exon size distribution and the origin of introns. Genetica 131:299–306

    Article  PubMed  CAS  Google Scholar 

  55. Dahl E, Kristiansen G, Gottlob K et al (2006) Molecular profiling of laser-microdissected matched tumor and normal breast tissue identifies karyopherin alpha2 as a potential novel prognostic marker in breast cancer. Clin Cancer Res 12:3950–3960

    Article  PubMed  CAS  Google Scholar 

  56. Gluz O, Wild P, Meiler R et al (2008) Nuclear karyopherin alpha2 expression predicts poor survival in patients with advanced breast cancer irrespective of treatment intensity. Int J Cancer 123:1433–1438

    Article  PubMed  CAS  Google Scholar 

  57. Suomela S, Cao L, Bowcock A, Saarialho-Kere U (2004) Interferon alpha-inducible protein 27 (IFI27) is upregulated in psoriatic skin and certain epithelial cancers. J Invest Dermatol 122:717–721

    Article  PubMed  CAS  Google Scholar 

  58. Wenzel J, Tomiuk S, Zahn S et al (2008) Transcriptional profiling identifies an interferon-associated host immune response in invasive squamous cell carcinoma of the skin. Int J Cancer 123:2605–2615

    Article  PubMed  CAS  Google Scholar 

  59. Badve S, Turbin D, Thorat MA, Morimiya A, Nielsen TO, Perou CM, Dunn S, Huntsman DG, Nakshatri H (2007) FOXA1 expression in breast cancer-correlation with luminal subtype A and survival. Clin Cancer Res 13:4415–4421

    Article  PubMed  CAS  Google Scholar 

  60. Habashy HO, Powe DG, Rakha EA, Ball G, Paish C, Gee J, Nicholson RI, Ellis IO (2008) Forkhead-box A1 (FOXA1) expression in breast cancer and its prognostic significance. Eur J Cancer 44:1541–1551

    Article  PubMed  CAS  Google Scholar 

  61. Mochizuki S, Okada Y (2007) ADAMs in cancer cell proliferation and progression. Cancer Sci 98:621–628

    Article  PubMed  CAS  Google Scholar 

  62. Rocks N, Paulissen G, El Hour M et al (2008) Emerging roles of ADAM and ADAMTS metalloproteinases in cancer. Biochimie 90:369–379

    Article  PubMed  CAS  Google Scholar 

  63. Kaida D, Berg MG, Younis I, Kasim M, Singh LN, Wan L, Dreyfuss G (2010) U1 snRNP protects pre-mRNAs from premature cleavage and polyadenylation. Nature 468:664–668

    Article  PubMed  CAS  Google Scholar 

  64. Sultan M, Schulz MH, Richard H et al (2008) A global view of gene activity and alternative splicing by deep sequencing of the human transcriptome. Science 321:956–960

    Article  PubMed  CAS  Google Scholar 

  65. Mortazavi A, Williams BA, McCue K, Schaeffer L, Wold B (2008) Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nat Methods 5:621–628

    Article  PubMed  CAS  Google Scholar 

  66. Wang ET, Sandberg R, Luo S, Khrebtukova I, Zhang L, Mayr C, Kingsmore SF, Schroth GP, Burge CB (2008) Alternative isoform regulation in human tissue transcriptomes. Nature 456:470–476

    Article  PubMed  CAS  Google Scholar 

  67. Lister R, O’Malley RC, Tonti-Filippini J, Gregory BD, Berry CC, Millar AH, Ecker JR (2008) Highly integrated single-base resolution maps of the epigenome in Arabidopsis. Cell 133:523–536

    Article  PubMed  CAS  Google Scholar 

  68. Wilhelm BT, Marguerat S, Watt S, Schubert F, Wood V, Goodhead I, Penkett CJ, Rogers J, Bahler J (2008) Dynamic repertoire of a eukaryotic transcriptome surveyed at single-nucleotide resolution. Nature 453:1239–1243

    Article  PubMed  CAS  Google Scholar 

  69. Cloonan N, Forrest AR, Kolle G et al (2008) Stem cell transcriptome profiling via massive-scale mRNA sequencing. Nat Methods 5:613–619

    Article  PubMed  CAS  Google Scholar 

  70. Okoniewski MJ, Miller CJ (2006) Hybridization interactions between probe sets in short oligo microarrays lead to spurious correlations. BMC Bioinformatics 7:276

    Article  PubMed  Google Scholar 

  71. Hoen PAt, Ariyurek Y, Thygesen HH, et al (2008) Deep sequencing-based expression analysis shows major advances in robustness, resolution and inter-lab portability over five microarray platforms. Nucleic Acids Res 36(21):e141

    Google Scholar 

  72. Parsons DW, Jones S, Zhang X et al (2008) An integrated genomic analysis of human glioblastoma multiforme. Science 321:1807–1812

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  74. Venables JP (2006) Unbalanced alternative splicing and its significance in cancer. Bioessays 28:378–386

    Article  PubMed  CAS  Google Scholar 

  75. Pajares MJ, Ezponda T, Catena R, Calvo A, Pio R, Montuenga LM (2007) Alternative splicing: an emerging topic in molecular and clinical oncology. Lancet Oncol 8:349–357

    Article  PubMed  CAS  Google Scholar 

  76. Moore MJ (2005) From birth to death: the complex lives of eukaryotic mRNAs. Science 309:1514–1518

    Article  PubMed  CAS  Google Scholar 

  77. Jan CH, Friedman RC, Ruby JG, Bartel DP (2011) Formation regulation and evolution of Caenorhabditis elegans 3’UTRs. Nature 469:97–101

    Article  PubMed  CAS  Google Scholar 

  78. Sandberg R, Neilson JR, Sarma A, Sharp PA, Burge CB (2008) Proliferating cells express mRNAs with shortened 3’ untranslated regions and fewer microRNA target sites. Science 320:1643–1647

    Article  PubMed  CAS  Google Scholar 

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Gencheva, M., Yang, L., Lin, GB., Lin, RJ. (2013). Detection of Alternatively Spliced or Processed RNAs in Cancer Using Oligonucleotide Microarray. In: Wu, J. (eds) RNA and Cancer. Cancer Treatment and Research, vol 158. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-31659-3_2

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  • DOI: https://doi.org/10.1007/978-3-642-31659-3_2

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