Epimutations, Inheritance and Causes of Aberrant DNA Methylation in Cancer

Hereditary Cancer in Clinical Practice

Rodney J Scott²  David Mossman¹ 

[1] Discipline of Medical Genetics, Faculty of Health, University of Newcastle, Hunter Medical Research Institute, NSW, Australia;Division of Genetics, Hunter Area Pathology Service, John Hunter Hospital, Newcastle, NSW, Australia

关键词: regulation of methylation;    epigenetic inheritance;    epimutation;    aberrant methylation;   

Others  :  812025
DOI  :  10.1186/1897-4287-4-2-75

 received in 2006-05-03, accepted in 2006-05-20,  发布年份 2006

【 摘 要 】

Epigenetic aberrations such as global hypomethylation and gene-specific hypermethylation are key events that underlie tumour development. Such scenarios are brought about by the loss of control of methylation patterns which typically are reversed in neoplasia in comparison to normal states. Despite the methylation process being termed epigenetic, suggesting that it is not a heritable condition, there is strong evidence in mouse models suggesting that epimutations within the germline may provide a mechanism through which methylation variations can be transmissible to offspring. The first half of the review will focus on the nature of methylation-induced gene silencing and transmission of this information through the germline. The latter half will focus on the cause of aberrant DNA methylation.

   

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Matsuzaki K, Deng G, Tanaka H, Kakar S, Miura S, Kim YS: The relationship between global methylation level, loss of heterozygosity, and microsatellite instability in sporadic colorectal cancer. Clin Cancer Res 2005, 11(24):8564-8569.
• [2]Weisenberger DJ, Campan M, Long TI, Kim M, Woods C, Fiala E, Ehrlich M, Laird PW: Analysis of repetitive element DNA methylation by MethyLight. Nucleic Acid Res 2005, 33:6823-6836.
• [3]Knudson A: Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci USA 1971, 68:820-823.
• [4]Ohtani-Fujita N, Dryja TP, Rapaport JM, Fujita T, Matsumura S, Ozasa K, Watanabe Y, Hayashi K, Maeda K, Kinoshita S, Matsumura T, Ohnishi Y, Hotta Y, Takahashi R, Kato MV, Ishizaki K, Sasaki MS, Horsthemke B, Minoda K, Sakai T: Hypermethylation in the retinoblastoma gene is associated with unilateral, sporadic retinoblastoma. Cancer Genet Cytogenet 1997, 98:43-49.
• [5]Prowse AH, Webster AR, Richards FM, Richard S, Olschwang S, Resche F, Affara NA, Maher ER: Somatic inactivation of the VHL gene in Von Hippel-Lindau disease tumours. Am J Hum Genet 1997, 60:765-771.
• [6]Herman JG, Umar A, Polyak K, Graff JR, Ahuja N, Issa JP, Markowitz S, Willson JK, Hamilton SR, Kinzler KW, Kane MF, Kolodner RD, Vogelstein B, Kunkel TA, Baylin SB: Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma. Proc Natl Acad Sci USA 1998, 95:6870-6875.
• [7]Geisler JP, Rathe JA, Manahan KJ, Geisler HE: Methylation: a second hit in the two-hit hypothesis. Eur J Gynaecol Oncol 2003, 24:361.
• [8]Myohanen SK, Baylin SB, Herman JG: Hypermethylation can selectively silence individual p16ink4A alleles in neoplasia. Cancer Res 1998, 58:591-593.
• [9]Furukawa T, Konishi F, Masubuchi S, Shitoh K, Nagai H, Tsukamoto T: Densely methylated MLH1 promoter correlates with decreased mRNA expression in sporadic colorectal cancers. Genes Chromosomes Cancer 2002, 35:1-10.
• [10]Suter CM, Martin DI, Ward RL: Germline epimutation of MLH1 in individuals with multiple cancers. Nat Genet 2004, 36:497-501.
• [11]Brucher BL, Geddert H, Langner C, Hofler H, Fink UR, Siewert J, Sarbia M: Hypermethylation of hMLH1, HPP1, p14 (ARF), p16 (INK4A) and APC in primary adenocarcinomas of the small bowel. Int J Cancer 2006, in press.
• [12]Lee S, Hwang KS, Lee HJ, Kim JS, Kang GH: Aberrant CpG island hypermethylation of multiple genes in colorectal neoplasia. Lab Invest 2004, 84:884-893.
• [13]Yanokura M, Banno K, Susumu N, Kawaguchi M, Kuwabara Y, Tsukazaki K, Aoki D: Hypemethylation in the p16 promoter region in the carcinogenesis of endometrial cancer in Japanese patients. Anticancer Res 2006, 26:851-856.
• [14]Dhawan D, Hamdy F, Rehman I, Patterson J, Cross S, Feeley K, Stephenson Y, Meuth M, Catto J: Evidence for the early onset of aberrant promoter methylation in urothelial carcinoma. J Pathol 2006, in press.
• [15]Bianco T, Chenevix-Trench G, Walsh DC, Cooper JE, Dobrovic A: Tumour specific distribution of BRCA1 promoter region methylation supports a pathogenic role in breast and ovarian cancer. Carcinogenesis 2000, 21:147-151.
• [16]Ma X, Yang Q, Wilson KT, Kundu N, Meltzer SJ, Fulton AM: Promoter methylation regulates cyclooxygenase expression in breast cancer. Breast Cancer research 2004, 6:R316-R321. BioMed Central Full Text
• [17]Cheng CW, Wu PE, Yu JC, Huang CS, Yue CT, Wu CW, Shen CY: Mechanisms of inactivation of E-cadherin in breast carcinoma: modification of the two hit hypothesis of tumour suppressor gene. Oncogene 2001, 20:3814-3823.
• [18]Fujii H, Biel MA, Zhou W, Weitzman SA, Baylin SB, Gabrielson F: Methylation of the HIC-1 candidate tumour suppressor gene in human breast cancer. Oncogene 1998, 16:2159-2164.
• [19]Roemer I, Reik W, Dean W, Klose J: Epigenetic Inheritance in the mouse. Curr Biol 1997, 7:277-280.
• [20]Gazzoli I, Loda M, Garber J, Syngal RD, Kolodner RD: A hereditary non polyposis colorectal carcinoma case associated with hyper methylation of the MLH1 gene in normal tissue and loss of heterozygosity of the unmethylated allele in the resulting microsatellite instability-high tumour. Cancer Res 2002, 62:3925-3928.
• [21]Miyakura Y, Sugano K, Akasu T, Yoshida T, Maekawa M, Saitoh S, Sasaki H, Nomizu T, Konishi F, Fujita S, Moriya Y, Nagai H: Extensive but hemiallelic methylation of hMLH1 promoter region in early-onset sporadic colon cancers with microsatellite instability. Clin Gastroenterol Hepatol 2004, 2:147-156.
• [22]Hitchins M, Williams R, Cheong K, Halani N, Ap Lin V, Packham D, Ku S, Buckle A, Hawkins N, Burn J, Gallinger S, Goldblatt J, Kirk J, Tomlinson I, Scott R, Spigelman A, Suter C, Martin D, Suthers G, Ward R: MLH1 germline epimutations as a factor in Hereditary non polyposis colorectal cancer. Gastroenterology 2005, 129:1392-1399.
• [23]Reik W, Dean W, Walter J: Epigenetic reprogramming in mammalian development. Science 2001, 293:1089-1093.
• [24]Esteller M, Corn PG, Baylin SB, Herman JG: A gene hypermethylation profile of human cancer. Cancer Res 2001, 61:3225-3229.
• [25]Melki JR, Warnecke P, Vincent PC, Clark SJ: Increased DNA methyltransferase expression in leukemia. Leukemia 1998, 12:311-316.
• [26]Jin F, Dowdy SC, Xiong Y, Eberhardt NL, Podratz KC, Jiang SW: Up-regulation of DNA methyltransferase 3B expression in endometrial cancers. Gynecol Oncol 2005, 96:531-538.
• [27]Belinsky SA, Nikula KJ, Baylin SB, Issa JP: Increased cytosine DNA-methyltransferase activity is target-cell-specific and an early event in lung cancer. Proc Natl Acad Sci USA 1996, 93:4045-4050.
• [28]Kimura F, Seifert HH, Florl AR, Santourlidis S, Steinhoff C, Swiatkowski S, Mahotka C, Gerharz CD, Schulz WA: Decrease of DNA methyltransferase 1 expression relative to cell proliferation in transitional cell carcinoma. Int J Cancer 2003, 104:568-578.
• [29]De Marzo AM, Marchi VL, Yang ES, Veeraswamy R, Lin X, Nelson WG: Abnormal regulation of DNA methyltransferase expression during colorectal carcinogenesis. Cancer Res 1999, 59:3855-3860.
• [30]Eads CA, Danenberg KD, Kawakami K, Saltz LB, Danenberg PV, Laird PW: CpG island hypermethylation in human colorectal tumours is not associated with DNA methyltransferase overexpression. Cancer Res 1999, 59:2302-2306.
• [31]Feltus FA, Lee EK, Costello JF, Plass C, Vertino PM: Predicting aberrant CpG island methylation. Proc Natl Acad of Sci USA 2003, 100:12253-12258.
• [32]Shi Y, Lan F, Matson C, Mulligan P, Whetstine JR, Cole PA, Casero RA, Shi Y: Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell 2004, 119:941-953.
• [33]Detich N, Theberge J, Szyf M: Promoter-specific activation and demethylation by MBD2/demethylase. J Biol Chem 2002, 277:35791-35794.
• [34]Szyf M, Bhattacharya SK: Measuring DNA demethylase activity in vitro. Methods Mol Biol 2002, 200:155-161.
• [35]Bhattacharya SK, Ramchandani S, Cervoni N, Szyf M: A mammalian protein with specific demethylase activity for mCpG DNA. Nature 1999, 397:579-583.
• [36]Ng HH, Zhang Y, Hendrich B, Johnson CA, Turner BM, Erdjument-Bromage H, Tempst P, Reinberg D, Bird A: The methyl-CpG binding protein MBD2 is a transcriptional repressor belonging to the MeCP1 fraction of histone deactylase complexes. Nat Genet 1999, 23:58-61.
• [37]Boeke J, Ammerpohl O, Kegel S, Moehren U, Renkawitz R: The minimal repression domain of MBD2b overlaps with the methyl-CpG-binding domain and binds directly to Sin3A. J Biol Chem 2000, 275:34963-34967.
• [38]Wade PA, Gegonne A, Jones PL, Ballestar E, Aubry F, Wolffe AP: Mi-2 complex couples DNA methylation to chromatin remodelling and histone deacetylation. Nat Genet 1999, 23:62-66.
• [39]Liu L, Wylie RC, Andrews LG, Tollefsbol TO: Aging, cancer and nutrition: the DNA methylation connection. Mech Ageing Dev 2003, 124:989-998.
• [40]McCabe DC, Caudill MA: DNA methylation, genomic silencing and links to nutrition and cancer. Nutr Rev 2005, 63:183-195.
• [41]Wu JC, Santi DV: On The mechanism and inhibition of DNA cytosine methyltransferases. Prog Clin Biol Res 1985, 198:119-129.
• [42]Kim YI: Folate and DNA methylation: a mechanistic link between folate deficiency and colorectal cancer? Cancer Epidemiol Biomarkers Prev 2004, 13:511-519.
• [43]Takiguchi M, Achanzar WE, Qu W, Li G, Waalkes MP: Effects of cadmium on DNA-(cytosine-5) methyltransferase activity and DNA methylation status during cadmium-induced cellular transformation. Exp Cell Res 2003, 286:355-365.
• [44]Costa M, Davidson TL, Chen H, Ke Q, Zhang P, Yan Y, Huang , Kluz T: Nickel carcinogenesis: epigenetics and hypoxia signalling. Mutat Res 2005, 592:79-88.
• [45]Bönsch D, Lenz B, Fiszer R, Frieling H, Kornhuber J, Bleich S: Lowered DNA methylatransferase (DNMT-3b) mRNA expression is associated with genomic DNA hypermethylation in patients with chronic alcoholism. In desktop folder.
• [46]Tollefsbol TO, Hutchison CA: Control of methylation spreading in synthetic DNA sequences by the murine DNA methyltransferase. J Mol Biol 1997, 269:494-504.