期刊论文详细信息
BMC Medical Genomics
High-throughput detection of aberrant imprint methylation in the ovarian cancer by the bisulphite PCR-Luminex method
Takahiro Arima4  Nobuo Yaegashi2  Kunihiko Nakai3  Junichi Sugawara2  Satoru Nagase2  Fumihiko Suzuki2  Akiko Sato2  Fumi Sato4  Naoko Miyauchi4  Hisato Kobayash1  Hiroaki Okae4  Hitoshi Hiura4 
[1] Department of BioScience, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502, Japan;Departments of Obstetrics and Gynecology, Tohoku University Graduate, School of Medicine, Sendai, Japan;Department of Development and Environmental Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan;Department of Informative Genetics, Environment and Genome Research Center, Tohoku University Graduate School of Medicine, 2-1 Seiryo-cho, Aoba-ku, Sendai 980-8575, Japan
关键词: LOI (loss of imprinting);    Bisulphite PCR-Luminex(BPL)method;    DNA methylation;    Ovarian cancer;    Genomic imprinting;   
Others  :  1135022
DOI  :  10.1186/1755-8794-5-8
 received in 2011-12-15, accepted in 2012-03-26,  发布年份 2012
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【 摘 要 】

Background

Aberrant DNA methylation leads to loss of heterozygosity (LOH) or loss of imprinting (LOI) as the first hit during human carcinogenesis. Recently we developed a new high-throughput, high-resolution DNA methylation analysis method, bisulphite PCR-Luminex (BPL), using sperm DNA and demonstrated the effectiveness of this novel approach in rapidly identifying methylation errors.

Results

In the current study, we applied the BPL method to the analysis of DNA methylation for identification of prognostic panels of DNA methylation cancer biomarkers of imprinted genes. We found that the BPL method precisely quantified the methylation status of specific DNA regions in somatic cells. We found a higher frequency of LOI than LOH. LOI at IGF2, PEG1 and H19 were frequent alterations, with a tendency to show a more hypermethylated state. We detected changes in DNA methylation as an early event in ovarian cancer. The degree of LOI (LOH) was associated with altered DNA methylation at IGF2/H19 and PEG1.

Conclusions

The relative ease of BPL method provides a practical method for use within a clinical setting. We suggest that DNA methylation of H19 and PEG1 differentially methylated regions (DMRs) may provide novel biomarkers useful for screening, diagnosis and, potentially, for improving the clinical management of women with human ovarian cancer.

【 授权许可】

   
2012 Hiura et al; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Russo A, Calo V, Bruno L, Rizzo S, Bazan V, Di Fede G: Hereditary ovarian cancer. Crit Rev Oncol Hematol 2009, 69:28-44.
  • [2]Balch C, Fang F, Matei DE, Huang TH, Nephew KP: Minireview: epigenetic changes in ovarian cancer. Endocrinology 2009, 150:4003-4011.
  • [3]Knudson AG: Genetics of human cancer. Annu Rev Genet 1986, 20:231-251.
  • [4]Jones PA, Laird PW: Cancer epigenetics comes of age. Nat Genet 1999, 21:163-167.
  • [5]Dryja TP, Mukai S, Petersen R, Rapaport JM, Walton D, Yandell DW: Parental origin of mutations of the retinoblastoma gene. Nature 1989, 339:556-558.
  • [6]Huff V, Meadows A, Riccardi VM, Strong LC, Saunders GF: Parental origin of de novo constitutional deletions of chromosomal band 11p13. Am J Hum Genet 1990, 47:155-160.
  • [7]Kajii T, Ohama K: Androgenetic origin of hydatidiform mole. Nature 1977, 268:633-634.
  • [8]Mutter GL: Teratoma genetics and stem cells: a review. Obstet Gynecol Surv 1987, 42:661-670.
  • [9]Feinberg AP: DNA methylation, genomic imprinting and cancer. Curr Top Microbiol Immunol 2000, 249:87-99.
  • [10]Joyce JA, Schofield PN: Genomic imprinting and cancer. Mol Pathol 1998, 51:185-190.
  • [11]Feinberg AP: Imprinting of a genomic domain of 11p15 and loss of imprinting in cancer: an introduction. Cancer Res 1999, 59:1743-1746.
  • [12]Zhang L, Volinia S, Bonome T, Calin GA, Greshock J, Yang N, et al.: Genomic and epigenetic alterations deregulate microRNA expression in human epithelial ovarian cancer. Proc Natl Acad Sci USA 2008, 105:7004-7009.
  • [13]Kohda T, Asai A, Kuroiwa Y, Kobayashi S, Aisaka K, Nagashima G, et al.: Tumour suppressor activity of human imprinted gene PEG3 in a glioma cell line. Genes Cells 2001, 6:237-247.
  • [14]Nakano S, Murakami K, Meguro M, Soejima H, Higashimoto K, Urano T, et al.: Expression profile of LIT1/KCNQ1OT1 and epigenetic status at the KvDMR1 in colorectal cancers. Cancer Sci 2006, 97:1147-1154.
  • [15]Kamikihara T, Arima T, Kato K, Matsuda T, Kato H, Douchi T, et al.: Epigenetic silencing of the imprinted gene ZAC by DNA methylation is an early event in the progression of human ovarian cancer. Int J Cancer 2005, 115:690-700.
  • [16]Surani MA: Imprinting and the initiation of gene silencing in the germ line. Cell 1998, 93:309-312.
  • [17]Koerner MV, Barlow DP: Genomic imprinting-an epigenetic gene-regulatory model. Curr Opin Genet Dev 2010, 20:164-170.
  • [18]Sato A, Hiura H, Okae H, Miyauchi N, Abe Y, Utsunomiya T, et al.: Assessing loss of imprint methylation in sperm from subfertile men using novel methylation polymerase chain reaction Luminex analysis. Fertil Steril 2011, 95:129-134.
  • [19]Reik W, Walter J: Genomic imprinting: parental influence on the genome. Nat Rev Genet 2001, 2:21-32.
  • [20]Murphy SK, Huang Z, Wen Y, Spillman MA, Whitaker RS, Simel LR, et al.: Frequent IGF2/H19 domain epigenetic alterations and elevated IGF2 expression in epithelial ovarian cancer. Molecular cancer research: MCR 2006, 4:283-292.
  • [21]Kobayashi H, Sato A, Otsu E, Hiura H, Tomatsu C, Utsunomiya T, et al.: Aberrant DNA methylation of imprinted loci in sperm from oligospermic patients. Hum Mol Genet 2007, 16:2542-2551.
  • [22]Toguchida J, Ishizaki K, Sasaki MS, Nakamura Y, Ikenaga M, Kato M, et al.: Preferential mutation of paternally derived RB gene as the initial event in sporadic osteosarcoma. Nature 1989, 338:156-158.
  • [23]Sato A, Otsu E, Negishi H, Utsunomiya T, Arima T: Aberrant DNA methylation of imprinted loci in superovulated oocytes. Hum Reprod 2007, 22:26-35.
  • [24]Olivier M, Eeles R, Hollstein M, Khan MA, Harris CC, Hainaut P: The IARC TP53 database: new online mutation analysis and recommendations to users. Hum Mutat 2002, 19:607-614.
  • [25]Obata K, Morland SJ, Watson RH, Hitchcock A, Chenevix-Trench G, Thomas EJ, et al.: Frequent PTEN/MMAC mutations in endometrioid but not serous or mucinous epithelial ovarian tumors. Cancer Res 1998, 58:2095-2097.
  • [26]Gorringe KL, Jacobs S, Thompson ER, Sridhar A, Qiu W, Choong DY, et al.: High-resolution single nucleotide polymorphism array analysis of epithelial ovarian cancer reveals numerous microdeletions and amplifications. Clin Cancer Res 2007, 13:4731-4739.
  • [27]Milde-Langosch K, Ocon E, Becker G, Loning T: p16/MTS1 inactivation in ovarian carcinomas: high frequency of reduced protein expression associated with hyper-methylation or mutation in endometrioid and mucinous tumors. Int J Cancer 1998, 79:61-65.
  • [28]Ludwig JA, Weinstein JN: Biomarkers in cancer staging, prognosis and treatment selection. Nat Rev Cancer 2005, 5:845-856.
  • [29]Ushijima T: Detection and interpretation of altered methylation patterns in cancer cells. Nat Rev Cancer 2005, 5:223-231.
  • [30]Cottrell SE, Laird PW: Sensitive detection of DNA methylation. Ann N Y Acad Sci 2003, 983:120-130.
  • [31]Li LC, Carroll PR, Dahiya R: Epigenetic changes in prostate cancer: implication for diagnosis and treatment. J Natl Cancer Inst 2005, 97:103-115.
  • [32]Bae YK, Brown A, Garrett E, Bornman D, Fackler MJ, Sukumar S, et al.: Hypermethylation in histologically distinct classes of breast cancer. Clin Cancer Res 2004, 10:5998-6005.
  • [33]Zochbauer-Muller S, Minna JD, Gazdar AF: Aberrant DNA methylation in lung cancer: biological and clinical implications. Oncologist 2002, 7:451-457.
  • [34]Henrique R, Jeronimo C: Molecular detection of prostate cancer: a role for GSTP1 hypermethylation. Eur Urol 2004, 46:660-669.
  • [35]Yang Q, Zage P, Kagan D, Tian Y, Seshadri R, Salwen HR, et al.: Association of epigenetic inactivation of RASSF1A with poor outcome in human neuroblastoma. Clin Cancer Res 2004, 10:8493-8500.
  • [36]Esteller M, Corn PG, Baylin SB, Herman JG: A gene hypermethylation profile of human cancer. Cancer Res 2001, 61:3225-3229.
  • [37]Costello JF, Fruhwald MC, Smiraglia DJ, Rush LJ, Robertson GP, Gao X, et al.: Aberrant CpG-island methylation has non-random and tumour-type-specific patterns. Nat Genet 2000, 24:132-138.
  • [38]Suzuki F, Akahira J, Miura I, Suzuki T, Ito K, Hayashi S, et al.: Loss of estrogen receptor beta isoform expression and its correlation with aberrant DNA methylation of the 5'-untranslated region in human epithelial ovarian carcinoma. Cancer Sci 2008, 99:2365-2372.
  • [39]Ueoka Y, Kato K, Kuriaki Y, Horiuchi S, Terao Y, Nishida J, et al.: Hepatocyte growth factor modulates motility and invasiveness of ovarian carcinomas via Ras-mediated pathway. Br J Cancer 2000, 82:891-899.
  • [40]Kikuchi R, Tsuda H, Kanai Y, Kasamatsu T, Sengoku K, Hirohashi S, et al.: Promoter hypermethylation contributes to frequent inactivation of a putative conditional tumor suppressor gene connective tissue growth factor in ovarian cancer. Cancer Res 2007, 67:7095-7105.
  • [41]Vambergue A, Fajardy I, Dufour P, Valat AS, Vandersippe M, Fontaine P, et al.: No loss of genomic imprinting of IGF-II and H19 in placentas of diabetic pregnancies with fetal macrosomia. Growth Horm IGF Res 2007, 17:130-136.
  • [42]Wylie AA, Murphy SK, Orton TC, Jirtle RL: Novel imprinted DLK1/GTL2 domain on human chromosome 14 contains motifs that mimic those implicated in IGF2/H19 regulation. Genome Res 2000, 10:1711-1718.
  • [43]Ogawa O, Eccles MR, Szeto J, McNoe LA, Yun K, Maw MA, et al.: Relaxation of insulin-like growth factor II gene imprinting implicated in Wilms' tumour. Nature 1993, 362:749-751.
  • [44]Maegawa S, Yoshioka H, Itaba N, Kubota N, Nishihara S, Shirayoshi Y, et al.: Epigenetic silencing of PEG3 gene expression in human glioma cell lines. Mol Carcinog 2001, 31:1-9.
  • [45]Pedersen IS, Dervan PA, Broderick D, Harrison M, Miller N, Delany E, et al.: Frequent loss of imprinting of PEG1/MEST in invasive breast cancer. Cancer Res 1999, 59:5449-5451.
  • [46]Higashimoto K, Soejima H, Yatsuki H, Katsuki T, Mukai T: An NsiI RFLP in the human long QT intronic transcript 1 (LIT1). J Hum Genet 2000, 45:96-97.
  • [47]Mitsuya K, Meguro M, Lee MP, Katoh M, Schulz TC, Kugoh H, et al.: An imprinted antisense RNA in the human KvLQT1 locus identified by screening for differentially expressed transcripts using monochromosomal hybrids. Hum Mol Genet 1999, 8:1209-1217.
  • [48]MacDonald HR, Wevrick R: The necdin gene is deleted in Prader-Willi syndrome and is imprinted in human and mouse. Hum Mol Genet 1997, 6:1873-1878.
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