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BMC Cancer
Published in: BMC Cancer 1/2011

Open Access 01-12-2011 | Research article

NMD and microRNA expression profiling of the HPCX1 locus reveal MAGEC1 as a candidate prostate cancer predisposition gene

Authors: Henna Mattila, Martin Schindler, Jarkko Isotalo, Tarja Ikonen, Mauno Vihinen, Hannu Oja, Teuvo LJ Tammela, Tiina Wahlfors, Johanna Schleutker

Published in: BMC Cancer | Issue 1/2011

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Abstract

Background

Several predisposition loci for hereditary prostate cancer (HPC) have been suggested, including HPCX1 at Xq27-q28, but due to the complex structure of the region, the susceptibility gene has not yet been identified.

Methods

In this study, nonsense-mediated mRNA decay (NMD) inhibition was used for the discovery of truncating mutations. Six prostate cancer (PC) patients and their healthy brothers were selected from a group of HPCX1-linked families. Expression analyses were done using Agilent 44 K oligoarrays, and selected genes were screened for mutations by direct sequencing. In addition, microRNA expression levels in the lymphoblastic cells were analyzed to trace variants that might alter miRNA expression and explain partly an inherited genetic predisposion to PC.

Results

Seventeen genes were selected for resequencing based on the NMD array, but no truncating mutations were found. The most interesting variant was MAGEC1 p.Met1?. An association was seen between the variant and unselected PC (OR = 2.35, 95% CI = 1.10-5.02) and HPC (OR = 3.38, 95% CI = 1.10-10.40). miRNA analysis revealed altogether 29 miRNAs with altered expression between the PC cases and controls. miRNA target analysis revealed that 12 of them also had possible target sites in the MAGEC1 gene. These miRNAs were selected for validation process including four miRNAs located in the X chromosome. The expressions of 14 miRNAs were validated in families that contributed to the significant signal differences in Agilent arrays.

Conclusions

Further functional studies are needed to fully understand the possible contribution of these miRNAs and MAGEC1 start codon variant to PC.
Appendix
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Literature
1.
2.
Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, Koskenvuo M, Pukkala E, Skytthe A, Hemminki K: Environmental and heritable factors in the causation of cancer--analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med. 2000, 343: 78-85. 10.1056/NEJM200007133430201.CrossRefPubMed
3.
Schaid DJ: The complex genetic epidemiology of prostate cancer. Hum Mol Genet. 2004, 13 (Spec No 1): R103-21.CrossRefPubMed
4.
Xu J, Meyers D, Freije D, Isaacs S, Wiley K, Nusskern D, Ewing C, Wilkens E, Bujnovszky P, Bova GS, Walsh P, Isaacs W, Schleutker J, Matikainen M, Tammela T, Visakorpi T, Kallioniemi OP, Berry R, Schaid D, French A, McDonnell S, Schroeder J, Blute M, Thibodeau S, Grönberg H, Emanuelsson M, Damber JE, Bergh A, Jonsson BA, Smith J, et al: Evidence for a prostate cancer susceptibility locus on the X chromosome. Nat Genet. 1998, 20: 175-179. 10.1038/2477.CrossRefPubMed
5.
Schleutker J, Matikainen M, Smith J, Koivisto P, Baffoe-Bonnie A, Kainu T, Gillanders E, Sankila R, Pukkala E, Carpten J, Stephan D, Tammela T, Brownstein M, Bailey-Wilson J, Trent J, Kallioniemi OP: A genetic epidemiological study of hereditary prostate cancer (HPC) in Finland: frequent HPCX linkage in families with late-onset disease. Clin Cancer Res. 2000, 6: 4810-4815.PubMed
6.
Baffoe-Bonnie AB, Smith JR, Stephan DA, Schleutker J, Carpten JD, Kainu T, Gillanders EM, Matikainen M, Teslovich TM, Tammela T, Sood R, Balshem AM, Scarborough SD, Xu J, Isaacs WB, Trent JM, Kallioniemi OP, Bailey-Wilson JE: A major locus for hereditary prostate cancer in Finland: localization by linkage disequilibrium of a haplotype in the HPCX region. Hum Genet. 2005, 117: 307-316. 10.1007/s00439-005-1306-z.CrossRefPubMed
7.
Stephan DA, Howell GR, Teslovich TM, Coffey AJ, Smith L, Bailey-Wilson JE, Malechek L, Gildea D, Smith JR, Gillanders EM, Schleutker J, Hu P, Steingruber HE, Dhami P, Robbins CM, Makalowska I, Carpten JD, Sood R, Mumm S, Reinbold R, Bonner TI, Baffoe-Bonnie A, Bubendorf L, Heiskanen M, Kallioniemi OP, Baxevanis AD, Joseph SS, Zucchi I, Burk RD, Isaacs W, et al: Physical and transcript map of the hereditary prostate cancer region at Xq27. Genomics. 2002, 79: 41-50. 10.1006/geno.2001.6681.CrossRefPubMed
8.
Kouprina N, Pavlicek A, Noskov VN, Solomon G, Otstot J, Isaacs W, Carpten JD, Trent JM, Schleutker J, Barrett JC, Jurka J, Larionov V: Dynamic structure of the SPANX gene cluster mapped to the prostate cancer susceptibility locus HPCX at Xq27. Genome Res. 2005, 15: 1477-1486. 10.1101/gr.4212705.CrossRefPubMedPubMedCentral
9.
Kouprina N, Noskov VN, Solomon G, Otstot J, Isaacs W, Xu J, Schleutker J, Larionov V: Mutational analysis of SPANX genes in families with X-linked prostate cancer. Prostate. 2007, 67: 820-828. 10.1002/pros.20561.CrossRefPubMed
10.
Culbertson MR: RNA surveillance. Unforeseen consequences for gene expression, inherited genetic disorders and cancer. Trends Genet. 1999, 15: 74-80. 10.1016/S0168-9525(98)01658-8.CrossRefPubMed
11.
Noensie EN, Dietz HC: A strategy for disease gene identification through nonsense-mediated mRNA decay inhibition. Nat Biotechnol. 2001, 19: 434-439. 10.1038/88099.CrossRefPubMed
12.
Ionov Y, Nowak N, Perucho M, Markowitz S, Cowell JK: Manipulation of nonsense mediated decay identifies gene mutations in colon cancer cells with microsatellite instability. Oncogene. 2004, 23: 639-645. 10.1038/sj.onc.1207178.CrossRefPubMed
13.
14.
Ambs S, Prueitt RL, Yi M, Hudson RS, Howe TM, Petrocca F, Wallace TA, Liu CG, Volinia S, Calin GA, Yfantis HG, Stephens RM, Croce CM: Genomic profiling of microRNA and messenger RNA reveals deregulated microRNA expression in prostate cancer. Cancer Res. 2008, 68: 6162-6170. 10.1158/0008-5472.CAN-08-0144.CrossRefPubMedPubMedCentral
15.
Ozen M, Creighton CJ, Ozdemir M, Ittmann M: Widespread deregulation of microRNA expression in human prostate cancer. Oncogene. 2008, 27: 1788-1793. 10.1038/sj.onc.1210809.CrossRefPubMed
16.
Baskerville S, Bartel DP: Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes. RNA. 2005, 11: 241-247. 10.1261/rna.7240905.CrossRefPubMedPubMedCentral
17.
Cropp CD, Simpson CL, Wahlfors T, Ha N, George A, Jones MS, Harper U, Ponciano-Jackson D, Green TA, Tammela TL, Bailey-Wilson J, Schleutker J: Genome-wide linkage scan for prostate cancer susceptibility in Finland: Evidence for a novel locus on 2q37.2 and confirmation of signal on 17q21-q22. Int J Cancer. 2011
18.
Schröder FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, Nelen V, Kwiatkowski M, Lujan M, Lilja H, Zappa M, Denis LJ, Recker F, Berenguer A, Määttänen L, Bangma CH, Aus G, Villers A, Rebillard X, van der Kwast T, Blijenberg BG, Moss SM, de Koning HJ, Auvinen A, ERSPC Investigators: Screening and prostate-cancer mortality in a randomized European study. N Engl J Med. 2009, 360: 1320-1328. 10.1056/NEJMoa0810084.CrossRefPubMed
19.
20.
Griffiths-Jones S, Saini HK, van Dongen S, Enright AJ: miRBase: tools for microRNA genomics. Nucleic Acids Res. 2008, 36: D154-8. 10.1093/nar/gkn221.CrossRefPubMed
21.
Mendell JT, Sharifi NA, Meyers JL, Martinez-Murillo F, Dietz HC: Nonsense surveillance regulates expression of diverse classes of mammalian transcripts and mutes genomic noise. Nat Genet. 2004, 36: 1073-1078. 10.1038/ng1429.CrossRefPubMed
22.
Pakkanen S, Baffoe-Bonnie AB, Matikainen MP, Koivisto PA, Tammela TL, Deshmukh S, Ou L, Bailey-Wilson JE, Schleutker J: Segregation analysis of 1,546 prostate cancer families in Finland shows recessive inheritance. Hum Genet. 2007, 121: 257-267. 10.1007/s00439-006-0310-2.CrossRefPubMedPubMedCentral
23.
Huusko P, Ponciano-Jackson D, Wolf M, Kiefer JA, Azorsa DO, Tuzmen S, Weaver D, Robbins C, Moses T, Allinen M, Hautaniemi S, Chen Y, Elkahloun A, Basik M, Bova GS, Bubendorf L, Lugli A, Sauter G, Schleutker J, Ozcelik H, Elowe S, Pawson T, Trent JM, Carpten JD, Kallioniemi OP, Mousses S: Nonsense-mediated decay microarray analysis identifies mutations of EPHB2 in human prostate cancer. Nat Genet. 2004, 36: 979-983. 10.1038/ng1408.CrossRefPubMed
24.
Bloethner S, Mould A, Stark M, Hayward NK: Identification of ARHGEF17, DENND2D, FGFR3, and RB1 mutations in melanoma by inhibition of nonsense-mediated mRNA decay. Genes Chromosomes Cancer. 2008, 47: 1076-1085. 10.1002/gcc.20598.CrossRefPubMed
25.
Ivanov I, Lo KC, Hawthorn L, Cowell JK, Ionov Y: Identifying candidate colon cancer tumor suppressor genes using inhibition of nonsense-mediated mRNA decay in colon cancer cells. Oncogene. 2007, 26: 2873-2884. 10.1038/sj.onc.1210098.CrossRefPubMed
26.
Rossi MR, Hawthorn L, Platt J, Burkhardt T, Cowell JK, Ionov Y: Identification of inactivating mutations in the JAK1, SYNJ2, and CLPTM1 genes in prostate cancer cells using inhibition of nonsense-mediated decay and microarray analysis. Cancer Genet Cytogenet. 2005, 161: 97-103. 10.1016/j.cancergencyto.2005.02.006.CrossRefPubMed
27.
Cui J, Staples MP, Hopper JL, English DR, McCredie MR, Giles GG: Segregation analyses of 1,476 population-based Australian families affected by prostate cancer. Am J Hum Genet. 2001, 68: 1207-1218. 10.1086/320114.CrossRefPubMedPubMedCentral
28.
Lucas S, De Smet C, Arden KC, Viars CS, Lethé B, Lurquin C, Boon T: Identification of a new MAGE gene with tumor-specific expression by representational difference analysis. Cancer Res. 1998, 58: 743-752.PubMed
29.
Zmuda JM, Cauley JA, Ferrell RE: Molecular epidemiology of vitamin D receptor gene variants. Epidemiol Rev. 2000, 22: 203-217.CrossRefPubMed
30.
Wolf M, Edgren H, Muggerud A, Kilpinen S, Huusko P, Sorlie T, Mousses S, Kallioniemi O: NMD microarray analysis for rapid genome-wide screen of mutated genes in cancer. Cell Oncol. 2005, 27: 169-173.PubMedPubMedCentral
31.
Sie L, Loong S, Tan EK: Utility of lymphoblastoid cell lines. J Neurosci Res. 2009, 87: 1953-9. 10.1002/jnr.22000.CrossRefPubMed
32.
Mattie MD, Benz CC, Bowers J, Sensinger K, Wong L, Scott GK, Fedele V, Ginzinger D, Getts R, Haqq C: Optimized high-throughput microRNA expression profiling provides novel biomarker assessment of clinical prostate and breast cancer biopsies. Mol Cancer. 2006, 5: 24-10.1186/1476-4598-5-24.CrossRefPubMedPubMedCentral
33.
Porkka KP, Pfeiffer MJ, Waltering KK, Vessella RL, Tammela TL, Visakorpi T: MicroRNA expression profiling in prostate cancer. Cancer Res. 2007, 67: 6130-6135. 10.1158/0008-5472.CAN-07-0533.CrossRefPubMed
34.
deVere White RW, Vinall RL, Tepper CG, Shi XB: MicroRNAs and their potential for translation in prostate cancer. Urol Oncol. 2009, 27: 307-311. 10.1016/j.urolonc.2009.01.004.CrossRefPubMedPubMedCentral
35.
Lutter D, Marr C, Krumsiek J, Lang EW, Theis FJ: Intronic microRNAs support their host genes by mediating synergistic and antagonistic regulatory effects. BMC Genomics. 2010, 11: 224-10.1186/1471-2164-11-224.CrossRefPubMedPubMedCentral
36.
Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O'Briant KC, Allen A, Lin DW, Urban N, Drescher CW, Knudsen BS, Stirewalt DL, Gentleman R, Vessella RL, Nelson PS, Martin DB, Tewari M: Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA. 2008, 105: 10513-18. 10.1073/pnas.0804549105.CrossRefPubMedPubMedCentral
37.
Lawrie CH, Gal S, Dunlop HM, Pushkaran B, Liggins AP, Pulford K, Banham AH, Pezzella F, Boultwood J, Wainscoat JS, Hatton CS, Harris AL: Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br J Haematol. 2008, 141: 672-675. 10.1111/j.1365-2141.2008.07077.x.CrossRefPubMed
38.
Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, Guo J, Zhang Y, Chen J, Guo X, Li Q, Li X, Wang W, Zhang Y, Wang J, Jiang X, Xiang Y, Xu C, Zheng P, Zhang J, Li R, Zhang H, Shang X, Gong T, Ning G, Wang J, Zen K, Zhang J, Zhang CY: Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008, 10: 997-1006.CrossRef
Metadata
Title
NMD and microRNA expression profiling of the HPCX1 locus reveal MAGEC1 as a candidate prostate cancer predisposition gene
Authors
Henna Mattila
Martin Schindler
Jarkko Isotalo
Tarja Ikonen
Mauno Vihinen
Hannu Oja
Teuvo LJ Tammela
Tiina Wahlfors
Johanna Schleutker
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2011
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-11-327

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