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===Transcriptional regulation in cancer=== {{main|Regulation of transcription in cancer}} The majority of gene [[Promoter (genetics)#CpG islands in promoters|promoters]] contain a [[CpG site#CpG islands|CpG island]] with numerous [[CpG site]]s.<ref name="pmid16432200">{{cite journal | vauthors = Saxonov S, Berg P, Brutlag DL | title = A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promoters | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 5 | pages = 1412β1417 | date = January 2006 | pmid = 16432200 | pmc = 1345710 | doi = 10.1073/pnas.0510310103 | doi-access = free | bibcode = 2006PNAS..103.1412S }}</ref> When many of a gene's promoter CpG sites are [[DNA methylation|methylated]] the gene becomes silenced.<ref name=Bird>{{cite journal | vauthors = Bird A | title = DNA methylation patterns and epigenetic memory | journal = Genes & Development | volume = 16 | issue = 1 | pages = 6β21 | date = January 2002 | pmid = 11782440 | doi = 10.1101/gad.947102 | doi-access = free }}</ref> Colorectal cancers typically have 3 to 6 [[Somatic evolution in cancer#Glossary|driver]] mutations and 33 to 66 [[Genetic hitchhiking|hitchhiker]] or passenger mutations.<ref name="pmid23539594">{{cite journal | vauthors = Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA, Kinzler KW | title = Cancer genome landscapes | journal = Science | volume = 339 | issue = 6127 | pages = 1546β1558 | date = March 2013 | pmid = 23539594 | pmc = 3749880 | doi = 10.1126/science.1235122 | bibcode = 2013Sci...339.1546V }}</ref> However, transcriptional silencing may be of more importance than mutation in causing progression to cancer. For example, in colorectal cancers about 600 to 800 genes are transcriptionally silenced by CpG island methylation (see [[regulation of transcription in cancer]]). Transcriptional repression in cancer can also occur by other [[Cancer epigenetics|epigenetic]] mechanisms, such as altered expression of [[MicroRNA#DNA repair and cancer|microRNAs]].<ref name="pmid24616890">{{cite journal | vauthors = Tessitore A, Cicciarelli G, Del Vecchio F, Gaggiano A, Verzella D, Fischietti M, Vecchiotti D, Capece D, Zazzeroni F, Alesse E | title = MicroRNAs in the DNA Damage/Repair Network and Cancer | journal = International Journal of Genomics | volume = 2014 | pages = 820248 | year = 2014 | pmid = 24616890 | pmc = 3926391 | doi = 10.1155/2014/820248 | doi-access = free }}</ref> In breast cancer, transcriptional repression of [[BRCA1]] may occur more frequently by over-transcribed microRNA-182 than by hypermethylation of the BRCA1 promoter (see [[BRCA1#Low expression of BRCA1 in breast and ovarian cancers|Low expression of BRCA1 in breast and ovarian cancers]]).
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