Editing BRCA2 (section)

==Epigenetic control==

Epigenetic alterations in expression of BRCA2 (causing over-expression or under-expression) are very frequent in sporadic cancers (see Table below) while mutations in BRCA2 are rarely found.<ref name="pmid8640236">{{cite journal |vauthors=Teng DH, Bogden R, Mitchell J, Baumgard M, Bell R, Berry S, Davis T, Ha PC, Kehrer R, Jammulapati S, Chen Q, Offit K, Skolnick MH, Tavtigian SV, Jhanwar S, Swedlund B, Wong AK, Kamb A |title=Low incidence of BRCA2 mutations in breast carcinoma and other cancers |journal=Nat. Genet. |volume=13 |issue=2 |pages=241–4 |year=1996 |pmid=8640236 |doi=10.1038/ng0696-241 |s2cid=9831745 }}</ref><ref name="pmid8640237">{{cite journal |vauthors=Miki Y, Katagiri T, Kasumi F, Yoshimoto T, Nakamura Y |title=Mutation analysis in the BRCA2 gene in primary breast cancers |journal=Nat. Genet. |volume=13 |issue=2 |pages=245–7 |year=1996 |pmid=8640237 |doi=10.1038/ng0696-245 |s2cid=3203046 }}</ref><ref name="pmid8640235">{{cite journal |vauthors=Lancaster JM, Wooster R, Mangion J, Phelan CM, Cochran C, Gumbs C, Seal S, Barfoot R, Collins N, Bignell G, Patel S, Hamoudi R, Larsson C, Wiseman RW, Berchuck A, Iglehart JD, Marks JR, Ashworth A, Stratton MR, Futreal PA |title=BRCA2 mutations in primary breast and ovarian cancers |journal=Nat. Genet. |volume=13 |issue=2 |pages=238–40 |year=1996 |pmid=8640235 |doi=10.1038/ng0696-238 |s2cid=26808443 }}</ref>

In non-small cell lung cancer, BRCA2 is epigenetically repressed by hypermethylation of the promoter.<ref name=Lee>{{cite journal |vauthors=Lee MN, Tseng RC, Hsu HS, Chen JY, Tzao C, Ho WL, Wang YC |title=Epigenetic inactivation of the chromosomal stability control genes BRCA1, BRCA2, and XRCC5 in non-small cell lung cancer |journal=Clin. Cancer Res. |volume=13 |issue=3 |pages=832–8 |year=2007 |pmid=17289874 |doi=10.1158/1078-0432.CCR-05-2694 |doi-access=free }}</ref>  In this case, promoter hypermethylation is significantly associated with low [[Messenger RNA|mRNA]] expression and low protein expression but not with loss of heterozygosity of the gene.

In sporadic ovarian cancer, an opposite effect is found.  BRCA2 promoter and 5'-UTR regions have relatively few or no methylated CpG dinucleotides in the tumor DNA compared with that of non-tumor DNA, and a significant correlation is found between hypomethylation and a >3-fold over-expression of BRCA2.<ref name=Chan>{{cite journal |vauthors=Chan KY, Ozçelik H, Cheung AN, Ngan HY, Khoo US |title=Epigenetic factors controlling the BRCA1 and BRCA2 genes in sporadic ovarian cancer |journal=Cancer Res. |volume=62 |issue=14 |pages=4151–6 |year=2002 |pmid=12124354 }}</ref>  This indicates that hypomethylation of the BRCA2 promoter and [[Five prime untranslated regions|5'-UTR regions]] leads to over-expression of BRCA2 mRNA.

One report indicated some epigenetic control of BRCA2 expression by the [[microRNA]]s miR-146a and miR-148a.<ref name="pmid25537514">{{cite journal |vauthors=Gu Y, Zhang M, Peng F, Fang L, Zhang Y, Liang H, Zhou W, Ao L, Guo Z |title=The BRCA1/2-directed miRNA signature predicts a good prognosis in ovarian cancer patients with wild-type BRCA1/2 |journal=Oncotarget |volume=6 |issue=4 |pages=2397–406 |year=2015 |pmid=25537514 |pmc=4385859 |doi=10.18632/oncotarget.2963 }}</ref>