MED12, the Mediator Complex Subunit 12 Gene, Is Mutated at High Frequency in Uterine Leiomyomas

被引：476

作者：

Makinen, Netta ^{[1
]}

Mehine, Miika ^{[1
]}

Tolvanen, Jaana ^{[1
]}

Kaasinen, Eevi ^{[1
]}

Li, Yilong ^{[1
]}

Lehtonen, Heli J. ^{[1
]}

Gentile, Massimiliano ^{[2
]}

Yan, Jian ^{[3
]}

Enge, Martin ^{[3
]}

Taipale, Minna ^{[1
,3
]}

Aavikko, Mervi ^{[1
]}

Katainen, Riku ^{[1
]}

Virolainen, Elina ^{[4
]}

Bohling, Tom ^{[4
,5
]}

Koski, Taru A. ^{[1
]}

Launonen, Virpi ^{[1
]}

Sjoberg, Jari ^{[6
]}

Taipale, Jussi ^{[1
,3
]}

Vahteristo, Pia ^{[1
]}

Aaltonen, Lauri A. ^{[1
]}

机构：

[1] Univ Helsinki, Genome Scale Biol Res Program, Dept Med Genet, FIN-00014 Helsinki, Finland

[2] Ctr Sci Ltd, Espoo 02101, Finland

[3] Karolinska Inst, Sci Life Lab, Dept Biosci & Nutr, S-14183 Stockholm, Sweden

[4] Univ Helsinki, Haartman Inst, Dept Pathol, FIN-00014 Helsinki, Finland

[5] Helsinki Univ Cent Hosp, Lab Hosp Dist Helsinki & Uusimaa, Helsinki 00029, Finland

[6] Helsinki Univ Cent Hosp, Dept Obstet & Gynecol, Helsinki 00029, Finland

来源：

SCIENCE | 2011年 / 334卷 / 6053期

基金：

芬兰科学院;

关键词：

FG SYNDROME; MEDIATOR; ETIOLOGY; FEATURES; COMPLEX;

D O I：

10.1126/science.1208930

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Uterine leiomyomas, or fibroids, are benign tumors that affect millions of women worldwide and that can cause considerable morbidity. To study the genetic basis of this tumor type, we examined 18 uterine leiomyomas derived from 17 different patients by exome sequencing and identified tumor-specific mutations in the mediator complex subunit 12 (MED12) gene in 10. Through analysis of 207 additional tumors, we determined that MED12 is altered in 70% (159 of 225) of tumors from a total of 80 patients. The Mediator complex is a 26-subunit transcriptional regulator that bridges DNA regulatory sequences to the RNA polymerase II initiation complex. All mutations resided in exon 2, suggesting that aberrant function of this region of MED12 contributes to tumorigenesis.

引用

页码：252 / 255

页数：4

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