Cross-Species Genomics Identifies TAF12, NFYC, and RAD54L as Choroid Plexus Carcinoma Oncogenes

Cancer Cell. 2015 May 11;27(5):712-27. doi: 10.1016/j.ccell.2015.04.005.

Abstract

Choroid plexus carcinomas (CPCs) are poorly understood and frequently lethal brain tumors with few treatment options. Using a mouse model of the disease and a large cohort of human CPCs, we performed a cross-species, genome-wide search for oncogenes within syntenic regions of chromosome gain. TAF12, NFYC, and RAD54L co-located on human chromosome 1p32-35.3 and mouse chromosome 4qD1-D3 were identified as oncogenes that are gained in tumors in both species and required for disease initiation and progression. TAF12 and NFYC are transcription factors that regulate the epigenome, whereas RAD54L plays a central role in DNA repair. Our data identify a group of concurrently gained oncogenes that cooperate in the formation of CPC and reveal potential avenues for therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • CCAAT-Binding Factor / genetics*
  • Carcinoma / genetics*
  • Carcinoma / pathology
  • Cell Proliferation / genetics
  • Choroid Plexus Neoplasms / genetics*
  • Choroid Plexus Neoplasms / pathology
  • Chromosome Mapping
  • DNA Helicases / genetics*
  • DNA Primers
  • DNA-Binding Proteins
  • Genomics*
  • Humans
  • Mice
  • Nuclear Proteins / genetics*
  • Oligonucleotide Array Sequence Analysis
  • Oncogenes*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Species Specificity
  • TATA-Binding Protein Associated Factors / genetics*

Substances

  • CCAAT-Binding Factor
  • DNA Primers
  • DNA-Binding Proteins
  • NFYC protein, human
  • Nuclear Proteins
  • TAF12 protein, human
  • TATA-Binding Protein Associated Factors
  • DNA Helicases
  • RAD54L protein, human

Supplementary concepts

  • Choroid Plexus Carcinoma

Associated data

  • GEO/GSE60899