Recurrent somatic mutations in <i>POLR2A</i> define a distinct subset of meningiomas


Clarke V. E., Harmanci A. S., Bai H., Youngblood M. W., Lee T. I., Baranoski J. F., ...Daha Fazla

NATURE GENETICS, cilt.48, sa.10, ss.1253-1259, 2016 (SCI-Expanded) identifier identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 48 Sayı: 10
  • Basım Tarihi: 2016
  • Doi Numarası: 10.1038/ng.3651
  • Dergi Adı: NATURE GENETICS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.1253-1259
  • Acıbadem Mehmet Ali Aydınlar Üniversitesi Adresli: Hayır

Özet

RNA polymerase II mediates the transcription of all protein-coding genes in eukaryotic cells, a process that is fundamental to life. Genomic mutations altering this enzyme have not previously been linked to any pathology in humans, which is a testament to its indispensable role in cell biology. On the basis of a combination of next-generation genomic analyses of 775 meningiomas, we report that recurrent somatic p.Gln403Lys or p.Leu438_His439del mutations in POLR2A, which encodes the catalytic subunit of RNA polymerase II (ref. 1), hijack this essential enzyme and drive neoplasia. POLR2A mutant tumors show dysregulation of key meningeal identity genes(2,3), including WNT6 and ZIC1/ZIC4. In addition to mutations in POLR2A, NF2, SMARCB1,TRAF7, KLF4, AKT1, PIK3CA, and SMO4-8, we also report somatic mutations in AKT3, PIK3R1, PRKAR1A, and SUFU in meningiomas. Our results identify a role for essential transcriptional machinery in driving tumorigenesis and define mutually exclusive meningioma subgroups with distinct clinical and pathological features.