Cooperative Epigenetic Modulation by Cancer Amplicon Genes
Cancer Cell, cilt.18, sa.6, ss.590-605, 2010 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 18 Sayı: 6
- Basım Tarihi: 2010
- Doi Numarası: 10.1016/j.ccr.2010.11.013
- Dergi Adı: Cancer Cell
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Sayfa Sayıları: ss.590-605
- Boğaziçi Üniversitesi Adresli: Hayır
Özet
Chromosome band 9p24 is frequently amplified in primary mediastinal B cell lymphoma (PMBL) and Hodgkin lymphoma (HL). To identify oncogenes in this amplicon, we screened an RNA interference library targeting amplicon genes and thereby identified JAK2 and the histone demethylase JMJD2C as essential genes in these lymphomas. Inhibition of JAK2 and JMJD2C cooperated in killing these lymphomas by decreasing tyrosine 41 phosphorylation and increasing lysine 9 trimethylation of histone H3, promoting heterochromatin formation. MYC, a major target of JAK2-mediated histone phosphorylation, was silenced after JAK2 and JMJD2C inhibition, with a corresponding increase in repressive chromatin. Hence, JAK2 and JMJD2C cooperatively remodel the PMBL and HL epigenome, offering a mechanistic rationale for the development of JAK2 and JMJD2C inhibitors in these diseases. © 2010 Elsevier Inc.