The 5p12 breast cancer susceptibility locus affects MRPS30 expression in estrogen-receptor positive tumors.
The 5p12 breast cancer susceptibility locus affects MRPS30 expression in estrogen-receptor positive tumors.
复制标题
DOI：
10.1016/j.molonc.2013.11.008
复制
发表时间：
2014-03
影响因子：
6.6
通讯作者：
Kristensen V
中科院分区：
文献类型：
--
作者：
Quigley DA;Fiorito E;Nord S;Van Loo P;Alnæs GG;Fleischer T;Tost J;Moen Vollan HK;Tramm T;Overgaard J;Bukholm IR;Hurtado A;Balmain A;Børresen-Dale AL;Kristensen V
Genome-wide association studies have identified numerous loci linked to breast cancer susceptibility, but the mechanism by which variations at these loci influence susceptibility is usually unknown. Some variants are only associated with particular clinical subtypes of breast cancer. Understanding how and why these variants influence subtype-specific cancer risk contributes to our understanding of cancer etiology. We conducted a genome-wide expression Quantitative Trait Locus (eQTL) study in a discovery set of 287 breast tumors and 97 normal mammary tissue samples and a replication set of 235 breast tumors. We found that the risk-associated allele of rs7716600 in the 5p12 estrogen receptor-positive (ER-positive) susceptibility locus was associated with elevated expression of the nearby gene MRPS30 exclusively in ER-positive tumors. We replicated this finding in 235 independent tumors. Further, we showed the rs7716600 risk genotype was associated with decreased MRPS30 promoter methylation exclusively in ER-positive breast tumors. In vitro studies in MCF-7 cells carrying the protective genotype showed that estrogen stimulation decreased MRPS30 promoter chromatin availability and mRNA levels. In contrast, in 600MPE cells carrying the risk genotype, estrogen increased MRPS30 expression and did not affect promoter availability. Our data suggest the 5p12 risk allele affects MRPS30 expression in estrogen-responsive tumor cells after tumor initiation by a mechanism affecting chromatin availability. These studies emphasize that the genetic architecture of breast cancer is context-specific, and integrated analysis of gene expression and chromatin remodeling in normal and tumor tissues will be required to explain the mechanisms of risk alleles.
登录
查看更多内容
DOI：
10.1158/1055-9965.epi-11-0569
发表时间：
2011-10
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Milne RL;Goode EL;García-Closas M;Couch FJ;Severi G;Hein R;Fredericksen Z;Malats N;Zamora MP;Arias Pérez JI;Benítez J;Dörk T;Schürmann P;Karstens JH;Hillemanns P;Cox A;Brock IW;Elliot G;Cross SS;Seal S;Turnbull C;Renwick A;Rahman N;Shen CY;Yu JC;Huang CS;Hou MF;Nordestgaard BG;Bojesen SE;Lanng C;Grenaker Alnæs G;Kristensen V;Børrensen-Dale AL;Hopper JL;Dite GS;Apicella C;Southey MC;Lambrechts D;Yesilyurt BT;Floris G;Leunen K;Sangrajrang S;Gaborieau V;Brennan P;McKay J;Chang-Claude J;Wang-Gohrke S;Radice P;Peterlongo P;Manoukian S;Barile M;Giles GG;Baglietto L;John EM;Miron A;Chanock SJ;Lissowska J;Sherman ME;Figueroa JD;Bogdanova NV;Antonenkova NN;Zalutsky IV;Rogov YI;Fasching PA;Bayer CM;Ekici AB;Beckmann MW;Brenner H;Müller H;Arndt V;Stegmaier C;Andrulis IL;Knight JA;Glendon G;Mulligan AM;Mannermaa A;Kataja V;Kosma VM;Hartikainen JM;Meindl A;Heil J;Bartram CR;Schmutzler RK;Thomas GD;Hoover RN;Fletcher O;Gibson LJ;dos Santos Silva I;Peto J;Nickels S;Flesch-Janys D;Anton-Culver H;Ziogas A;Sawyer E;Tomlinson I;Kerin M;Miller N;Schmidt MK;Broeks A;Van 't Veer LJ;Tollenaar RA;Pharoah PD;Dunning AM;Pooley KA;Marme F;Schneeweiss A;Sohn C;Burwinkel B;Jakubowska A;Lubinski J;Jaworska K;Durda K;Kang D;Yoo KY;Noh DY;Ahn SH;Hunter DJ;Hankinson SE;Kraft P;Lindstrom S;Chen X;Beesley J;Hamann U;Harth V;Justenhoven C;GENICA Network;Winqvist R;Pylkäs K;Jukkola-Vuorinen A;Grip M;Hooning M;Hollestelle A;Oldenburg RA;Tilanus-Linthorst M;Khusnutdinova E;Bermisheva M;Prokofieva D;Farahtdinova A;Olson JE;Wang X;Humphreys MK;Wang Q;Chenevix-Trench G;kConFab Investigators;AOCS Group;Easton DF
通讯作者：
Easton DF
影响因子：
64.5
作者：
Li Q;Seo JH;Stranger B;McKenna A;Pe'er I;Laframboise T;Brown M;Tyekucheva S;Freedman ML
通讯作者：
Freedman ML
影响因子：
64.5
作者：
Kim, Tae Hoon;Abdullaev, Ziedulla K.;Ren, Bing
通讯作者：
Ren, Bing
影响因子：
64.8
作者：
Curtis, Christina;Shah, Sohrab P.;Chin, Suet-Feung;Turashvili, Gulisa;Rueda, Oscar M.;Dunning, Mark J.;Speed, Doug;Lynch, Andy G.;Samarajiwa, Shamith;Yuan, Yinyin;Graef, Stefan;Ha, Gavin;Haffari, Gholamreza;Bashashati, Ali;Russell, Roslin;McKinney, Steven;Langerod, Anita;Green, Andrew;Provenzano, Elena;Wishart, Gordon;Pinder, Sarah;Watson, Peter;Markowetz, Florian;Murphy, Leigh;Ellis, Ian;Purushotham, Arnie;Borresen-Dale, Anne-Lise;Brenton, James D.;Tavare, Simon;Caldas, Carlos;Aparicio, Samuel
通讯作者：
Aparicio, Samuel
DOI：
10.1126/science.1222794
发表时间：
2012-09-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Maurano MT;Humbert R;Rynes E;Thurman RE;Haugen E;Wang H;Reynolds AP;Sandstrom R;Qu H;Brody J;Shafer A;Neri F;Lee K;Kutyavin T;Stehling-Sun S;Johnson AK;Canfield TK;Giste E;Diegel M;Bates D;Hansen RS;Neph S;Sabo PJ;Heimfeld S;Raubitschek A;Ziegler S;Cotsapas C;Sotoodehnia N;Glass I;Sunyaev SR;Kaul R;Stamatoyannopoulos JA
通讯作者：
Stamatoyannopoulos JA