Editing Malignant transformation (section)

==DNA repair gene silencing==
{{main article|DNA methylation in cancer|Regulation of transcription in cancer}}

Silencing of a DNA repair gene by [[DNA methylation in cancer|hypermethylation]] or other [[Cancer epigenetics|epigenetic]] alteration appears to be a frequent step in progression to cancer.  As summarized in a review,{{Citation needed|date=December 2019|reason=removed citation to predatory publisher content}} promoter hypermethylation of  DNA repair gene ''[[O-6-methylguanine-DNA methyltransferase|MGMT]]'' occurs in 93% of bladder cancers, 88% of stomach cancers, 74% of thyroid cancers, 40%-90% of colorectal cancers and 50% of brain cancers.  In addition, promoter hypermethylation of DNA repair genes ''[[LIG4]]'', ''[[NEIL1]]'', ''[[Ataxia telangiectasia mutated|ATM]]'', ''[[MLH1]]'' or ''[[FANCB]]'' occurs at frequencies of between 33% and 82% in one or more of [[head and neck cancer]]s, [[non-small-cell lung carcinoma|non-small-cell lung cancer]]s or [[non-small-cell lung carcinoma|non-small-cell lung cancer]] squamous cell carcinomas.   Further, the article [[Werner syndrome ATP-dependent helicase]] indicates the DNA repair gene ''[[Werner syndrome ATP-dependent helicase|WRN]]'' has a promoter that is often hypermethylated in a variety of cancers, with ''WRN'' hypermethylation occurring in 11% to 38% of [[colorectal cancer|colorectal]], [[head and neck cancer|head and neck]], [[stomach cancer|stomach]], [[prostate cancer|prostate]], [[Breast cancer|breast]], [[thyroid cancer|thyroid]], [[non-Hodgkin lymphoma]], [[chondrosarcoma]] and [[osteosarcoma]] cancers.

Such silencing likely acts similarly to a germ-line mutation in a DNA repair gene, and predisposes the cell and its descendants to progression to cancer.<ref name=Jin>{{cite book |vauthors=Jin B, Robertson KD |chapter=DNA Methyltransferases, DNA Damage Repair, and Cancer |title=Epigenetic Alterations in Oncogenesis |volume=754 |pages=3–29 |year=2013 |pmid=22956494 |pmc=3707278 |doi=10.1007/978-1-4419-9967-2_1 |series=Advances in Experimental Medicine and Biology |isbn=978-1-4419-9966-5 }}</ref>  Another review<ref name="pmid23671730">{{cite journal |vauthors=Bernstein C, Nfonsam V, Prasad AR, Bernstein H |title=Epigenetic field defects in progression to cancer |journal=World J Gastrointest Oncol |volume=5 |issue=3 |pages=43–9 |year=2013 |pmid=23671730 |pmc=3648662 |doi=10.4251/wjgo.v5.i3.43 |doi-access=free }}</ref> points out that when a gene necessary for DNA repair is epigenetically silenced, DNA repair would tend to be deficient and DNA damages can accumulate.  Increased DNA damage can cause increased errors during DNA synthesis, leading to mutations that give rise to cancer.