Individual and combined effects of DNA methylation and copy number alterations on miRNA expression in breast tumors

Genome Biology

Volumn 14, Issue 11, 2013, Pages

  Aure, Miriam R ^a,b   Leivonen, Suvi Katri ^a,b   Fleischer, Thomas ^a,b   Zhu, Qian ^c   Overgaard, Jens ^d   Alsner, Jan ^d   Tramm, Trine ^d   Louhimo, Riku ^e   Alnæs, Grethe I G ^a,b   Perälä, Merja ^f   Busato, Florence ^g   Touleimat, Nizar ^g   Tost, Jörg ^g   Børresen Dale, Anne Lise ^a,b   Hautaniemi, Sampsa ^e   Troyanskaya, Olga G ^c,h   Lingjærde, Ole C ^b,i   Sahlberg, Kristine K ^a,b,j   Kristensen, Vessela N ^a,b,k  

^a OSLO UNIVERSITY HOSPITAL   (Norway)

^b UNIVERSITY OF OSLO   (Norway)

^c Princeton University   (United States)

^d AARHUS UNIVERSITY HOSPITAL   (Denmark)

^e UNIVERSITY OF HELSINKI   (Finland)

^f VTT TECHNICAL RESEARCH CENTRE OF FINLAND   (Finland)

^g CENTRE NATIONAL DE GÉNOTYPAGE   (France)

^h PRINCETON UNIVERSITY   (United States)

ⁱ UNIVERSITY OF OSLO   (Norway)

^j VESTRE VIKEN HOSPITAL TRUST   (Norway)

^k AKERSHUS UNIVERSITY HOSPITAL   (Norway)

more..

Author keywords

[No Author keywords available]

Indexed keywords

MICRORNA; MICRORNA 148B 3P; MICRORNA 151A 5P; MICRORNA 21 3P; MICRORNA LET 7E 3P; PROTEIN KINASE B; UNCLASSIFIED DRUG;

APOPTOSIS; ARTICLE; BREAST CANCER; CANCER CELL CULTURE; CANCER PROGNOSIS; CELL PROLIFERATION; CELL SURVIVAL; CELL VIABILITY; CONTROLLED STUDY; DNA METHYLATION; ENZYME PHOSPHORYLATION; GENE DOSAGE; GENE EXPRESSION; GENETIC ASSOCIATION; HUMAN; HUMAN TISSUE; MAJOR CLINICAL STUDY; MOLECULAR PATHOLOGY; PHENOTYPE; RNA SEQUENCE; SEQUENCE ANALYSIS; BREAST TUMOR; COPY NUMBER VARIATION; DNA REPLICATION; FEMALE; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; COHORT ANALYSIS; IN VITRO STUDY; NUCLEOTIDE SEQUENCE; PROTEIN PHOSPHORYLATION;

BREAST NEOPLASMS; DNA COPY NUMBER VARIATIONS; DNA METHYLATION; DNA REPLICATION; FEMALE; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; MICRORNAS;

EID: 84887706233     PISSN: None     EISSN: 1474760X     Source Type: Journal    
DOI: 10.1186/gb-2013-14-11-r126     Document Type: Article

References (94)

1. Ding XC, Weiler J, Grosshans H. Regulating the regulators: mechanisms controlling the maturation of microRNAs. Trends Biotechnol 2009, 27:27-36. 10.1016/j.tibtech.2008.09.006, 19012978.
2. Friedman RC, Farh KK-H, Burge CB, Bartel DP. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res 2009, 19:92-105. 2612969, 18955434.
3. Mukherji S, Ebert MS, Zheng GXY, Tsang JS, Sharp PA, van Oudenaarden A. MicroRNAs can generate thresholds in target gene expression. Nat Genet 2011, 43:854-859. 10.1038/ng.905, 3163764, 21857679.
4. Enerly E, Steinfeld I, Kleivi K, Leivonen S-K, Aure MR, Russnes HG, Rønneberg JA, Johnsen H, Navon R, Rødland E, Mäkelä R, Naume B, Perälä M, Kallioniemi O, Kristensen VN, Yakhini Z, Børresen Dale AL. miRNA-mRNA Integrated Analysis Reveals Roles for miRNAs in Primary Breast Tumors. PLoS ONE 2011, 6:e16915. 10.1371/journal.pone.0016915, 3043070, 21364938.
5. Iorio MV, Ferracin M, Liu C-G, Veronese A, Spizzo R, Sabbioni S, Magri E, Pedriali M, Fabbri M, Campiglio M, Ménard S, Palazzo JP, Rosenberg A, Musiani P, Volinia S, Nenci I, Calin GA, Querzoli P, Negrini M, Croce CM. MicroRNA gene expression deregulation in human breast cancer. Cancer Res 2005, 65:7065-7070. 10.1158/0008-5472.CAN-05-1783, 16103053.
6. Qian P, Zuo Z, Wu Z, Meng X, Li G, Wu Z, Zhang W, Tan S, Pandey V, Yao Y, Wang P, Zhao L, Wang J, Wu Q, Song E, Lobie PE, Yin Z, Zhu T. Pivotal role of reduced let-7 g expression in breast cancer invasion and metastasis. Cancer Res 2011, 71:6463-6474. 10.1158/0008-5472.CAN-11-1322, 21868760.
7. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR. MicroRNA expression profiles classify human cancers. Nature 2005, 435:834-838. 10.1038/nature03702, 15944708.
8. Ferraro L, Ravo M, Nassa G, Tarallo R, De Filippo M, Giurato G, Cirillo F, Stellato C, Silvestro S, Cantarella C, Rizzo F, Cimino D, Friard O, Biglia N, De Bortoli M, Cicatiello L, Nola E, Weisz A. Effects of oestrogen on microRNA expression in hormone-responsive breast cancer cells. Horm Cancer 2012, 3:65-78. 10.1007/s12672-012-0102-1, 22274890.
9. Leivonen S-K, Makela R, Ostling P, Kohonen P, Haapa-Paananen S, Kleivi K, Enerly E, Aakula A, Hellstrom K, Sahlberg N, Kristensen VN, Borresen-Dale AL, Saviranta P, Perala M, Kallioniemi O. Protein lysate microarray analysis to identify microRNAs regulating estrogen receptor signaling in breast cancer cell lines. Oncogene 2009, 28:3926-3936. 10.1038/onc.2009.241, 19684618.
10. Maillot G, Lacroix-Triki M, Pierredon S, Gratadou L, Schmidt S, Bénès V, Roché H, Dalenc F, Auboeuf D, Millevoi S, Vagner S. Widespread estrogen-dependent repression of microRNAs involved in breast tumor cell growth. Cancer Res 2009, 69:8332-8340. 10.1158/0008-5472.CAN-09-2206, 19826037.
11. Shi W, Gerster K, Alajez NM, Tsang J, Waldron L, Pintilie M, Hui AB, Sykes J, P'ng C, Miller N, McCready D, Fyles A, Liu F-F. MicroRNA-301 mediates proliferation and invasion in human breast cancer. Cancer Res 2011, 71:2926-2937. 10.1158/0008-5472.CAN-10-3369, 21393507.
12. Mitra D, Das PM, Huynh FC, Jones FE. Jumonji/ARID1 B (JARID1B) protein promotes breast tumor cell cycle progression through epigenetic repression of microRNA let-7e. J Biol Chem 2011, 286:40531-40535. 10.1074/jbc.M111.304865, 3220509, 21969366.
13. Tavazoie SF, Alarcon C, Oskarsson T, Padua D, Wang Q, Bos PD, Gerald WL, Massague J. Endogenous human microRNAs that suppress breast cancer metastasis. Nature 2008, 451:147-152. 10.1038/nature06487, 2782491, 18185580.
14. Lujambio A, Calin GA, Villanueva A, Ropero S, Sánchez-Cépedes M, Blanco D, Montuenga LM, Rossi S, Nicoloso MS, Faller WJ, Gallagher WM, Eccles SA, Croce CM, Esteller M. A microRNA DNA methylation signature for human cancer metastasis. Proc Natl Acad Sci U S A 2008, 105:13556-13561. 10.1073/pnas.0803055105, 2528872, 18768788.
15. Wee EJH, Peters K, Nair SS, Hulf T, Stein S, Wagner S, Bailey P, Lee SY, Qu WJ, Brewster B, French JD, Dobrovic A, Francis GD, Clark SJ, Brown MA. Mapping the regulatory sequences controlling 93 breast cancer-associated miRNA genes leads to the identification of two functional promoters of the Hsa-mir-200b cluster, methylation of which is associated with metastasis or hormone receptor status in advanced breast cancer. Oncogene 2012, 31:4182-4195. 10.1038/onc.2011.584, 3448136, 22231446.
16. Yu F, Jiao Y, Zhu Y, Wang Y, Zhu J, Cui X, Liu Y, He Y, Park E-Y, Zhang H, Lv X, Ma K, Su F, Park JH, Song E. MicroRNA 34c gene down-regulation via DNA methylation promotes self-renewal and epithelial-mesenchymal transition in breast tumor-initiating cells. J Biol Chem 2011, 287:465-473. 3249099, 22074923.
17. Croce CM. Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet 2009, 10:704-714. 10.1038/nrg2634, 3467096, 19763153.
18. Shen J, Xia W, Khotskaya YB, Huo L, Nakanishi K, Lim S-O, Du Y, Wang Y, Chang W-C, Chen C-H, Hsu JL, Wu Y, Lam YC, James BP, Liu X, Liu C-G, Patel DJ, Hung M-C. EGFR modulates microRNA maturation in response to hypoxia through phosphorylation of AGO2. Nature 2013, 497:383-387. 10.1038/nature12080, 23636329.
19. Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, Aldler H, Rattan S, Keating M, Rai K. Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA 2002, 99:15524-15529. 10.1073/pnas.242606799, 137750, 12434020.
20. Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M, Croce CM. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA 2004, 101:2999-3004. 10.1073/pnas.0307323101, 365734, 14973191.
21. Ding J, Huang S, Wu S, Zhao Y, Liang L, Yan M, Ge C, Yao J, Chen T, Wan D, Wang H, Gu J, Yao M, Li J, Tu H, He X. Gain of miR-151 on chromosome 8q24.3 facilitates tumour cell migration and spreading through downregulating RhoGDIA. Nat Cell Biol 2010, 12:390-399. 10.1038/ncb2039, 20305651.
22. Serrano NA, Xu C, Liu Y, Wang P, Fan W, Upton MP, Houck JR, Lohavanichbutr P, Kao M, Zhao LP, Schwartz SM, Chen C, Méndez E. Integrative analysis in oral squamous cell carcinoma reveals DNA copy number-associated miRNAs dysregulating target genes. Otolaryngol Head Neck Surg 2012, 147:501-508. 10.1177/0194599812442490, 22470160.
23. Dvinge H, Git A, Graf S, Salmon-Divon M, Curtis C, Sottoriva A, Zhao Y, Hirst M, Armisen J, Miska EA, Chin S-F, Provenzano E, Turashvili G, Green A, Ellis I, Aparicio S, Caldas C. The shaping and functional consequences of the microRNA landscape in breast cancer. Nature 2013, 497:378-382. 10.1038/nature12108, 23644459.
24. Gal-Yam EN, Saito Y, Egger G, Jones PA. Cancer epigenetics: modifications, screening, and therapy. Annu Rev Med 2008, 59:267-280. 10.1146/annurev.med.59.061606.095816, 17937590.
25. Suzuki H, Maruyama R, Yamamoto E, Kai M. DNA methylation and microRNA dysregulation in cancer. Mol Oncol 2012, 6:567-578. 10.1016/j.molonc.2012.07.007, 22902148.
26. Cheung HH, Lee TL, Davis AJ, Taft DH, Rennert OM, Chan WY. Genome-wide DNA methylation profiling reveals novel epigenetically regulated genes and non-coding RNAs in human testicular cancer. Br J Cancer 2010, 102:419-427. 10.1038/sj.bjc.6605505, 2816664, 20051947.
27. Kozaki K, Inazawa J. Tumor-suppressive microRNA silenced by tumor-specific DNA hypermethylation in cancer cells. Cancer Sci 2012, 103:837-845. 10.1111/j.1349-7006.2012.02236.x, 22320679.
28. Lehmann U, Hasemeier B, Christgen M, Müller M, Römermann D, Länger F, Kreipe H. Epigenetic inactivation of microRNA gene hsa-mir-9-1 in human breast cancer. J Pathol 2008, 214:17-24. 10.1002/path.2251, 17948228.
29. Neves R, Scheel C, Weinhold S, Honisch E, Iwaniuk K, Trompeter H-I, Niederacher D, Wernet P, Santourlidis S, Uhrberg M. Role of DNA methylation in miR-200c/141 cluster silencing in invasive breast cancer cells. BMC Res Notes 2010, 3:219. 10.1186/1756-0500-3-219, 3161370, 20682048.
30. Radpour R, Barekati Z, Kohler C, Schumacher MM, Grussenmeyer T, Jenoe P, Hartmann N, Moes S, Letzkus M, Bitzer J, Lefkovits I, Staedtler F, Zhong XY. Integrated epigenetics of human breast cancer: synoptic investigation of targeted genes, microRNAs and proteins upon demethylation treatment. PLoS ONE 2011, 6:e27355. 10.1371/journal.pone.0027355, 3208622, 22076154.
31. Zhang Y, Yan L-X, Wu Q-N, Du Z-M, Chen J, Liao D-Z, Huang M-Y, Hou J-H, Wu Q-L, Zeng M-S, Huang W-L, Zeng Y-X, Shao JY. miR-125b is methylated and functions as a tumor suppressor by regulating the ETS1 proto-oncogene in human invasive breast cancer. Cancer Res 2011, 71:3552-3562. 10.1158/0008-5472.CAN-10-2435, 21444677.
32. Vrba L, Muñoz-Rodríguez J, Stampfer MR, Futscher BW. miRNA gene promoters are frequent targets of aberrant DNA methylation in human breast cancer. PLoS ONE 2013, 8:e54398. 10.1371/journal.pone.0054398, 3547033, 23342147.
33. Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 2005, 120:15-20. 10.1016/j.cell.2004.12.035, 15652477.
34. Krzywinski MI, Schein JE, Birol I, Connors J, Gascoyne R, Horsman D, Jones SJ, Marra MA. Circos: an information aesthetic for comparative genomics. Genome Res 2009, 19:1639-1645. 10.1101/gr.092759.109, 2752132, 19541911.
35. Bergamaschi A, Kim YH, Wang P, Sørlie T, Hernandez-Boussard T, Lonning PE, Tibshirani R, Børresen-Dale A-L, Pollack JR. Distinct patterns of DNA copy number alteration are associated with different clinicopathological features and gene-expression subtypes of breast cancer. Genes Chromosomes Cancer 2006, 45:1033-1040. 10.1002/gcc.20366, 16897746.
36. Ventura A, Young AG, Winslow MM, Lintault L, Meissner A, Erkeland SJ, Newman J, Bronson RT, Crowley D, Stone JR, Jaenisch R, Sharp PA, Jacks T. Targeted deletion reveals essential and overlapping functions of the miR-17-92 family of miRNA clusters. Cell 2008, 132:875-886. 10.1016/j.cell.2008.02.019, 2323338, 18329372.
37. Kim K, Chadalapaka G, Lee SO, Yamada D, Sastre-Garau X, Defossez PA, Park YY, Lee JS, Safe S. Identification of oncogenic microRNA-17-92/ZBTB4/specificity protein axis in breast cancer. Oncogene 2012, 31:1034-1044. 10.1038/onc.2011.296, 3288192, 21765466.
38. Griffiths-Jones S, Grocock RJ, van Dongen S, Bateman A, Enright AJ. miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acid Res 2006, 34:D140-D144. 10.1093/nar/gkj112, 1347474, 16381832.
39. Blenkiron C, Goldstein L, Thorne N, Spiteri I, Chin S-F, Dunning M, Barbosa-Morais N, Teschendorff A, Green A, Ellis I, Tavare S, Caldas C, Miska E. MicroRNA expression profiling of human breast cancer identifies new markers of tumor subtype. Genome Biol 2007, 8:R214. 10.1186/gb-2007-8-10-r214, 2246288, 17922911.
40. Tamura M, Gu J, Danen EHJ, Takino T, Miyamoto S, Yamada KM. PTEN interactions with focal adhesion kinase and suppression of the extracellular matrix-dependent phosphatidylinositol 3-kinase/Akt cell survival pathway. J Biol Chem 1999, 274:20693-20703. 10.1074/jbc.274.29.20693, 10400703.
41. Du Z, Fei T, Verhaak RGW, Su Z, Zhang Y, Brown M, Chen Y, Liu XS. Integrative genomic analyses reveal clinically relevant long noncoding RNAs in human cancer. Nat Struct Mol Biol 2013, 20:908-913. 10.1038/nsmb.2591, 23728290.
42. Dong X-Y, Guo P, Boyd J, Sun X, Li Q, Zhou W, Dong J-T. Implication of snoRNA U50 in human breast cancer. J Genet Genomics 2009, 36:447-454. 10.1016/S1673-8527(08)60134-4, 2854654, 19683667.
43. Git A, Dvinge H, Salmon-Divon M, Osborne M, Kutter C, Hadfield J, Bertone P, Caldas C. Systematic comparison of microarray profiling, real-time PCR, and next-generation sequencing technologies for measuring differential microRNA expression. RNA 2010, 16:991-1006. 10.1261/rna.1947110, 2856892, 20360395.
44. Louhimo R, Hautaniemi S. CNAmet: an R package for integrating copy number, methylation and expression data. Bioinformatics 2011, 27:887-888. 10.1093/bioinformatics/btr019, 21228048.
45. Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SAJR, Behjati S, Biankin AV, Bignell GR, Bolli N, Borg A, Borresen-Dale A-L, Boyault S, Burkhardt B, Butler AP, Caldas C, Davies HR, Desmedt C, Eils R, Eyfjord JE, Foekens JA, Greaves M, Hosoda F, Hutter B, Ilicic T, Imbeaud S, Imielinsk M, Jager N, Jones DTW, Jones D, Knappskog S, Kool M, et al. Signatures of mutational processes in human cancer. Nature 2013, 500:415-421. 10.1038/nature12477, 23945592.
46. Yu F, Deng H, Yao H, Liu Q, Su F, Song E. Mir-30 reduction maintains self-renewal and inhibits apoptosis in breast tumor-initiating cells. Oncogene 2010, 29:4194-4204. 10.1038/onc.2010.167, 20498642.
47. Martinez I, Cazalla D, Almstead LL, Steitz JA, DiMaio D. miR-29 and miR-30 regulate B-Myb expression during cellular senescence. Proc Natl Acad Sci USA 2010, 108:522-527. 3021067, 21187425.
48. Hertel J, Lindemeyer M, Missal K, Fried C, Tanzer A, Flamm C, Hofacker I, Stadler P, The Students of Bioinformatics Computer Labs 2004 and 2005 The expansion of the metazoan microRNA repertoire. BMC Genomics 2006, 7:25. 10.1186/1471-2164-7-25, 1388199, 16480513, The Students of Bioinformatics Computer Labs 2004 and 2005.
49. O'Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT. c-Myc-regulated microRNAs modulate E2F1 expression. Nature 2005, 435:839-843. 10.1038/nature03677, 15944709.
50. Zhao Z-N, Bai J-X, Zhou Q, Yan B, Qin W-W, Jia L-T, Meng Y-L, Jin B-Q, Yao L-B, Wang T, Yang A-G. TSA suppresses miR-106b-93-25 cluster expression through downregulation of MYC and inhibits proliferation and induces apoptosis in human EMC. PLoS ONE 2012, 7:e45133. 10.1371/journal.pone.0045133, 3446970, 23028803.
51. Scott GK, Goga A, Bhaumik D, Berger CE, Sullivan CS, Benz CC. Coordinate Suppression of ERBB2 and ERBB3 by Enforced Expression of Micro-RNA miR-125a or miR-125b. J Biol Chem 2007, 282:1479-1486.
52. Sampath J, Sun D, Kidd VJ, Grenet J, Gandhi A, Shapiro LH, Wang Q, Zambetti GP, Schuetz JD. Mutant p53 cooperates with ETS and selectively up-regulates human MDR1 not MRP1. J Biol Chem 2001, 276:39359-39367. 10.1074/jbc.M103429200, 11483599.
53. Farazi TA, Horlings HM, ten Hoeve JJ, Mihailovic A, Halfwerk H, Morozov P, Brown M, Hafner M, Reyal F, van Kouwenhove M, Kreike B, Sie D, Hovestadt V, Wessels LFA, van de Vijver MJ, Tuschl T. MicroRNA sequence and expression analysis in breast tumors by deep sequencing. Cancer Res 2011, 71:4443-4453. 10.1158/0008-5472.CAN-11-0608, 3129492, 21586611.
54. Kamalakaran S, Varadan V, Giercksky Russnes HE, Levy D, Kendall J, Janevski A, Riggs M, Banerjee N, Synnestvedt M, Schlichting E, Kåresen R, Shama Prasada K, Rotti H, Rao R, Rao L, Eric Tang M-H, Satyamoorthy K, Lucito R, Wigler M, Dimitrova N, Naume B, Borresen-Dale A-L, Hicks JB. DNA methylation patterns in luminal breast cancers differ from non-luminal subtypes and can identify relapse risk independent of other clinical variables. Mol Oncol 2011, 5:77-92. 10.1016/j.molonc.2010.11.002, 21169070.
55. Tahiri A, Leivonen SK, Lüders T, Steinfeld I, Ragle Aure M, Geisler J, Mäkelä R, Nord S, Riis ML, Yakhini Z, Kleivi Sahlberg K, Børresen-Dale AL, Perälä M, Bukholm IR, Kristensen VN. Deregulation of cancer-related miRNAs is a common event in both benign and malignant human breast tumors. Carcinogenesis in press.
56. Chen L, Li Y, Fu Y, Peng J, Mo M-H, Stamatakos M, Teal CB, Brem RF, Stojadinovic A, Grinkemeyer M, McCaffrey TA, Man Y-G, Fu SW. Role of deregulated microRNAs in breast cancer progression using FFPE tissue. PLoS ONE 2013, 8:e54213. 10.1371/journal.pone.0054213, 3553092, 23372687.
57. Biasiolo M, Sales G, Lionetti M, Agnelli L, Todoerti K, Bisognin A, Coppe A, Romualdi C, Neri A, Bortoluzzi S. Impact of host genes and strand selection on miRNA and miRNA* expression. PLoS ONE 2011, 6:e23854. 10.1371/journal.pone.0023854, 3166117, 21909367.
58. Yan L-X, Huang X-F, Shao Q, Huang MAY, Deng L, Wu Q-L, Zeng Y-X, Shao J-Y. MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinical stage, lymph node metastasis and patient poor prognosis. RNA 2008, 14:2348-2360. 10.1261/rna.1034808, 2578865, 18812439.
59. Haverty PM, Fridlyand J, Li L, Getz G, Beroukhim R, Lohr S, Wu TD, Cavet G, Zhang Z, Chant J. High-resolution genomic and expression analyses of copy number alterations in breast tumors. Genes Chromosomes Cancer 2008, 47:530-542. 10.1002/gcc.20558, 18335499.
60. Han M, Liu M, Wang Y, Chen X, Xu J, Sun Y, Zhao L, Qu H, Fan Y, Wu C. Antagonism of miR-21 reverses epithelial-mesenchymal transition and cancer stem cell phenotype through AKT/ERK1/2 inactivation by targeting PTEN. PLoS ONE 2012, 7:e39520. 10.1371/journal.pone.0039520, 3382593, 22761812.
61. Yamanaka Y, Tagawa H, Takahashi N, Watanabe A, Guo Y-M, Iwamoto K, Yamashita J, Saitoh H, Kameoka Y, Shimizu N, Ichinohasama R, Sawada K-I. Aberrant overexpression of microRNAs activate AKT signaling via down-regulation of tumor suppressors in natural killer-cell lymphoma/leukemia. Blood 2009, 114:3265-3275. 10.1182/blood-2009-06-222794, 19641183.
62. Roush S, Slack FJ. The let-7 family of microRNAs. Trends Cell Biol 2008, 18:505-516. 10.1016/j.tcb.2008.07.007, 18774294.
63. Takamizawa J, Konishi H, Yanagisawa K, Tomida S, Osada H, Endoh H, Harano T, Yatabe Y, Nagino M, Nimura Y, Mitsudomi T, Takahashi T. Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res 2004, 64:3753-3756. 10.1158/0008-5472.CAN-04-0637, 15172979.
64. Nadiminty N, Tummala R, Lou W, Zhu Y, Shi XB, Zou JX, Chen H, Zhang J, Chen X, Luo J, de Vere White RW, Kung HJ, Evans CP, Gao AC. MicroRNA let-7c is downregulated in prostate cancer and suppresses prostate cancer growth. PLoS ONE 2012, 7:e32832. 10.1371/journal.pone.0032832, 3316551, 22479342.
65. Loo LWM, Grove DI, Williams EM, Neal CL, Cousens LA, Schubert EL, Holcomb IN, Massa HF, Glogovac J, Li CI, Malone KE, Daling JR, Delrow JJ, Trask BJ, Hsu L, Porter PL. Array comparative genomic hybridization analysis of genomic alterations in breast cancer subtypes. Cancer Res 2004, 64:8541-8549. 10.1158/0008-5472.CAN-04-1992, 15574760.
66. Nakao M, Shigeto Kawauchi S, Uchiyama T, Adachi J, Ito H, Chochi Y, Furuya T, Oga O, Sasaki K. DNA copy number aberrations associated with the clinicopathological features of colorectal cancers: Identification of genomic biomarkers by array-based comparative genomic hybridization. Oncol Rep 2011, 25:6.
67. Kim SW, Kim JW, Kim YT, Kim JH, Kim S, Yoon BS, Nam EJ, Kim HY. Analysis of chromosomal changes in serous ovarian carcinoma using high-resolution array comparative genomic hybridization: Potential predictive markers of chemoresistant disease. Genes Chromosomes Cancer 2007, 46:1-9. 10.1002/gcc.20384, 17044060.
68. Duursma AM, Kedde M, Schrier M, le Sage C, Agami R. miR-148 targets human DNMT3b protein coding region. RNA 2008, 14:872-877. 10.1261/rna.972008, 2327368, 18367714.
69. Cuk K, Zucknick M, Heil J, Madhavan D, Schott S, Turchinovich A, Arlt D, Rath M, Sohn C, Benner A, Junkermann H, Schneeweiss A, Burwinkel B. Circulating microRNAs in plasma as early detection markers for breast cancer. Int J Cancer 2012, 132:1602-1612.
70. Cimino D, De Pitta C, Orso F, Zampini M, Casara S, Penna E, Quaglino E, Forni M, Damasco C, Pinatel E, Ponzone R, Romualdi C, Brisken C, De Bortoli M, Biglia N, Provero P, Lanfranchi G, Taverna D. miR148b is a major coordinator of breast cancer progression in a relapse-associated microRNA signature by targeting ITGA5, ROCK1, PIK3CA, NRAS, and CSF1. FASEB J 2012, 27:1223-1235.
71. The R Development Core Team R: A Language and Environment for Statistical Computing 2011, Vienna, Austria: R Foundation for Statistical Computing, The R Development Core Team.
72. Naume B, Borgen E, Kvalheim G, Kåresen R, Qvist H, Sauer T, Kumar T, Nesland JM. Detection of isolated tumor cells in bone marrow in early-stage breast carcinoma patients. Clin Cancer Res 2001, 7:4122-4129.
73. Sorlie T, Wang Y, Xiao C, Johnsen H, Naume B, Samaha R, Borresen-Dale A-L. Distinct molecular mechanisms underlying clinically relevant subtypes of breast cancer: gene expression analyses across three different platforms. BMC Genomics 2006, 7:127. 10.1186/1471-2164-7-127, 1489944, 16729877.
74. Naume B, Zhao X, Synnestvedt M, Borgen E, Russnes HG, Lingjærde OC, Strømberg M, Wiedswang G, Kvalheim G, Kåresen R, Nesland JM, Børresen-Dale A-L, Sørlie T. Presence of bone marrow micrometastasis is associated with different recurrence risk within molecular subtypes of breast cancer. Mol Oncol 2007, 1:160-171. 10.1016/j.molonc.2007.03.004, 19383292.
75. Myhre S, Mohammed H, Tramm T, Alsner J, Finak G, Park M, Overgaard J, Børresen-Dale A-L, Frigessi A, Sørlie T. In silico ascription of gene expression differences to tumor and stromal cells in a model to study impact on breast cancer outcome. PLoS ONE 2010, 5:e14002. 10.1371/journal.pone.0014002, 2988804, 21124964.
76. Overgaard M, Hansen PS, Overgaard J, Rose C, Andersson M, Bach F, Kjaer M, Gadeberg CC, Mouridsen HT, Jensen M-B, Zedeler K. Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. N Engl J Med 1997, 337:949-955. 10.1056/NEJM199710023371401, 9395428.
77. Overgaard M, Jensen M-B, Overgaard J, Hansen PS, Rose C, Andersson M, Kamby C, Kjaer M, Gadeberg CC, Rasmussen BB, Blichert-Toft M, Mouridsen HT. Postoperative radiotherapy in high-risk postmenopausal breast-cancer patients given adjuvant tamoxifen: Danish Breast Cancer Cooperative Group DBCG 82c randomised trial. The Lancet 1999, 353:1641-1648.
78. Riis M, Luders T, Nesbakken A-J, Vollan H, Kristensen V, Bukholm I. Expression of BMI-1 and Mel-18 in breast tissue - a diagnostic marker in patients with breast cancer. BMC Cancer 2010, 10:686. 10.1186/1471-2407-10-686, 3013088, 21162745.
79. Touleimat N, Tost J. Complete pipeline for Infinium® Human Methylation 450 K BeadChip data processing using subset quantile normalization for accurate DNA methylation estimation. Epigenomics 2012, 4:325-341. 10.2217/epi.12.21, 22690668.
80. Sandoval J, Heyn H, Moran S, Serra-Musach J, Pujana MA, Bibikova M, Esteller M. Validation of a DNA methylation microarray for 450,000 CpG sites in the human genome. Epigenetics 2011, 6:692-702. 10.4161/epi.6.6.16196, 21593595.
81. Tost J, Gut IG. DNA methylation analysis by pyrosequencing. Nat Protoc 2007, 2:2265-2275. 10.1038/nprot.2007.314, 17853883.
82. Nordgard SH, Johansen FE, Alnæs GIG, Bucher E, Syvänen A-C, Naume B, Børresen-Dale A-L, Kristensen VN. Genome-wide analysis identifies 16q deletion associated with survival, molecular subtypes, mRNA expression, and germline haplotypes in breast cancer patients. Genes Chromosomes Cancer 2008, 47:680-696. 10.1002/gcc.20569, 18398821.
83. Myhre S, Lingjærde O-C, Hennessy BT, Aure MR, Carey MS, Alsner J, Tramm T, Overgaard J, Mills GB, Børresen-Dale A-L, Sørlie T. Influence of DNA copy number and mRNA levels on the expression of breast cancer related proteins. Mol Oncol 2013, 7:704-718. 10.1016/j.molonc.2013.02.018, 23562353.
84. Nilsen G, Liestol K, Loo PV, Moen Vollan HK, Eide M, Rueda O, Chin S-F, Russell R, Baumbusch L, Caldas C, Borresen-Dale A-L, Lingjaerde OC. Copynumber: efficient algorithms for single- and multi-track copy number segmentation. BMC Genomics 2012, 13:591. 10.1186/1471-2164-13-591, 3582591, 23442169.
85. Kent WJ, Sugnet CW, Furey TS, Roskin KM, Pringle TH, Zahler AM, Haussler D. The Human Genome Browser at UCSC. Genome Res 2002, 12:996-1006. 186604, 12045153.
86. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc 1995, 57:289-300.
87. Brooks SC, Locke ER, Soule HD. Estrogen receptor in a human cell line (MCF-7) from breast carcinoma. J Biol Chem 1973, 248:6251-6253.
88. Soule H, Vazguez J, Long A, Albert S, Brennan M. A human cell line from a pleural effusion derived from a breast carcinoma. J Natl Cancer Inst 1973, 51:1409-1416.
89. Tanner M, Kapanen AI, Junttila T, Raheem O, Grenman S, Elo J, Elenius K, Isola J. Characterization of a novel cell line established from a patient with Herceptin-resistant breast cancer. Mol Cancer Ther 2004, 3:1585-1592.
90. Kurebayashi J, Otsuki T, Tang CK, Kurosumi M, Yamamoto S, Tanaka K, Mochizuki M, Nakamura H, Soono H. Isolation and characterization of a new human breast cancer cell line, KPL-4, expressing the Erb B family receptors and interleukin-6. Br J Cancer 1999, 79:707-717. 10.1038/sj.bjc.6690114, 2362677, 10070858.
91. Leivonen S-K, Sahlberg KK, Mäkelä R, Due EU, Kallioniemi O, Børresen-Dale A-L, Perälä M. High-throughput screens identify microRNAs essential for HER2 positive breast cancer cell growth. Mol Oncol 2013, 7891:00141-00145.
92. Boutros M, Bras L, Huber W. Analysis of cell-based RNAi screens. Genome Biol 2006, 7:R66. 10.1186/gb-2006-7-7-r66, 1779553, 16869968.
93. IPA - Ingenuity Pathway Analysis. [http://www.ingenuity.com/].
94. SEEK - Search-based Exploration of Expression Compendium. [http://seek.princeton.edu].