title: Identification of genomic aberrations in hemangioblastoma by droplet digital PCR and SNP microarray highlights novel candidate genes and pathways for pathogenesis.
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.
authors.affiliation: Pediatric Hemato-Oncology, Edmond and Lilly Safra Children's Hospital and Cancer Research Center, Sheba Medical Center, Tel Hashomer affiliated to the Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel. ruty.shai@sheba.health.gov.il.
authors.forename: Ruty
authors.initials: R
authors.lastname: Mehrian-Shai
authors.affiliation: Pediatric Hemato-Oncology, Edmond and Lilly Safra Children's Hospital and Cancer Research Center, Sheba Medical Center, Tel Hashomer affiliated to the Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel. michal@droren.co.il.
authors.forename: Michal
authors.initials: M
authors.lastname: Yalon
authors.affiliation: Pediatric Hemato-Oncology, Edmond and Lilly Safra Children's Hospital and Cancer Research Center, Sheba Medical Center, Tel Hashomer affiliated to the Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel. itaimoshe@gmail.com.
authors.forename: Itai
authors.initials: I
authors.lastname: Moshe
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Iris.Barshack@sheba.health.gov.il.|Institute of Pathology, Sheba Medical Center, Tel Hashomer, Israel. Iris.Barshack@sheba.health.gov.il.
authors.forename: Iris
authors.initials: I
authors.lastname: Barshack
authors.affiliation: Institute of Pathology, Sheba Medical Center, Tel Hashomer, Israel. Dvora.Nass@sheba.health.gov.il.
authors.forename: Dvorah
authors.initials: D
authors.lastname: Nass
authors.affiliation: Pediatric Hemato-Oncology, Edmond and Lilly Safra Children's Hospital and Cancer Research Center, Sheba Medical Center, Tel Hashomer affiliated to the Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel. Jasmine.Jacob@sheba.health.gov.il.
authors.forename: Jasmine
authors.initials: J
authors.lastname: Jacob
authors.affiliation: Pediatric Hemato-Oncology, Edmond and Lilly Safra Children's Hospital and Cancer Research Center, Sheba Medical Center, Tel Hashomer affiliated to the Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel. Chen.Gefen@sheba.health.gov.il.
authors.forename: Chen
authors.initials: C
authors.lastname: Dor
authors.affiliation: Division of Tropical Health and Medicine, James Cook University, Townsville, QLD, Australia. Juergen.reichardt@jcu.edu.au.
authors.forename: Juergen K V
authors.initials: JK
authors.lastname: Reichardt
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. sconsts@netvision.net.il.|Department of Pediatric Neurosurgery, Dana Children's Hospital, Tel-Aviv-Sourasky Medical Center, Tel-Aviv, Israel. sconsts@netvision.net.il.
authors.forename: Shlomi
authors.initials: S
authors.lastname: Constantini
authors.affiliation: Pediatric Hemato-Oncology, Edmond and Lilly Safra Children's Hospital and Cancer Research Center, Sheba Medical Center, Tel Hashomer affiliated to the Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel. amost@post.tau.ac.il.|Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. amost@post.tau.ac.il.
authors.forename: Amos
authors.initials: A
authors.lastname: Toren
mesh_terms: D000328:Adult; D000368:Aged; D049109:Cell Proliferation / Q000235:genetics; D002869:Chromosome Aberrations; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D018325:Hemangioblastoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction / Q000379:methods; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics
chemical_list: D035683:MicroRNAs; D009363:Neoplasm Proteins