Identification of genomic aberrations in hemangioblastoma by droplet digital PCR and SNP microarray highlights novel candidate genes and pathways for pathogenesis

BMC Genomics. 2016 Jan 14:17:56. doi: 10.1186/s12864-016-2370-6.

Abstract

Background: The genetic mechanisms underlying hemangioblastoma development are still largely unknown. We used high-resolution single nucleotide polymorphism microarrays and droplet digital PCR analysis to detect copy number variations (CNVs) in total of 45 hemangioblastoma tumors.

Results: We identified 94 CNVs with a median of 18 CNVs per sample. The most frequently gained regions were on chromosomes 1 (p36.32) and 7 (p11.2). These regions contain the EGFR and PRDM16 genes. Recurrent losses were located at chromosome 12 (q24.13), which includes the gene PTPN11.

Conclusions: Our findings provide the first high-resolution genome-wide view of chromosomal changes in hemangioblastoma and identify 23 candidate genes: EGFR, PRDM16, PTPN11, HOXD11, HOXD13, FLT3, PTCH, FGFR1, FOXP1, GPC3, HOXC13, HOXC11, MKL1, CHEK2, IRF4, GPHN, IKZF1, RB1, HOXA9, and micro RNA, such as hsa-mir-196a-2 for hemangioblastoma pathogenesis. Furthermore, our data implicate that cell proliferation and angiogenesis promoting pathways may be involved in the molecular pathogenesis of hemangioblastoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cell Proliferation / genetics
  • Chromosome Aberrations
  • DNA Copy Number Variations / genetics*
  • Female
  • Genetic Association Studies
  • Hemangioblastoma / genetics*
  • Hemangioblastoma / pathology
  • Humans
  • Loss of Heterozygosity / genetics*
  • Male
  • MicroRNAs / genetics
  • Middle Aged
  • Neoplasm Proteins / genetics*
  • Oligonucleotide Array Sequence Analysis
  • Polymerase Chain Reaction / methods
  • Polymorphism, Single Nucleotide / genetics
  • Signal Transduction / genetics

Substances

  • MicroRNAs
  • Neoplasm Proteins