JARID1B 是乳腺癌中管腔谱系驱动的癌基因。
JARID1B is a luminal lineage-driving oncogene in breast cancer.
机构信息
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard School of Public Health, Boston, MA 02115, USA.
出版信息
Cancer Cell. 2014 Jun 16;25(6):762-77. doi: 10.1016/j.ccr.2014.04.024.
Recurrent mutations in histone-modifying enzymes imply key roles in tumorigenesis, yet their functional relevance is largely unknown. Here, we show that JARID1B, encoding a histone H3 lysine 4 (H3K4) demethylase, is frequently amplified and overexpressed in luminal breast tumors and a somatic mutation in a basal-like breast cancer results in the gain of unique chromatin binding and luminal expression and splicing patterns. Downregulation of JARID1B in luminal cells induces basal genes expression and growth arrest, which is rescued by TGFβ pathway inhibitors. Integrated JARID1B chromatin binding, H3K4 methylation, and expression profiles suggest a key function for JARID1B in luminal cell-specific expression programs. High luminal JARID1B activity is associated with poor outcome in patients with hormone receptor-positive breast tumors.
组蛋白修饰酶的反复突变暗示其在肿瘤发生中的关键作用，但它们的功能相关性在很大程度上尚不清楚。在这里，我们表明，编码组蛋白 H3 赖氨酸 4（H3K4）去甲基化酶的 JARID1B 在腔细胞性乳腺癌中经常扩增和过表达，并且基底样乳腺癌中的体细胞突变导致独特的染色质结合和腔表达和剪接模式。在腔细胞中下调 JARID1B 会诱导基底基因的表达和生长停滞，而 TGFβ 途径抑制剂可挽救这一现象。整合的 JARID1B 染色质结合、H3K4 甲基化和表达谱表明 JARID1B 在腔细胞特异性表达程序中具有关键功能。高腔 JARID1B 活性与激素受体阳性乳腺癌患者的不良预后相关。
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