Identification of genomic aberrations in hemangioblastoma by droplet digital PCR and SNP microarray highlights novel candidate genes and pathways for pathogenesis. (December 2016)

• Record Type: Journal Article
• Authors: Mehrian-Shai, Ruty; Yalon, Michal; Moshe, Itai; Barshack, Iris; Nass, Dvorah; Jacob, Jasmine; Dor, Chen; Reichardt, Juergen; Constantini, Shlomi; Toren, Amos
• Is Part Of: BMC genomics. Volume 17:Number 1(2016)
• Page Start: 1
• Page End: 11
• Publication Date: 2016-12
• Subjects: Hemangioblastoma -- CGH -- digital PCR -- cancer; Genomes -- Periodicals; Gene mapping -- Periodicals; Genomics -- Periodicals; Base Sequence -- Periodicals; Chromosome Mapping -- Periodicals; Genetic Techniques -- Periodicals; Sequence Analysis, DNA -- Periodicals; 572.8605
• DOI: 10.1186/s12864-016-2370-6
• Languages: English
• ISSNs: 1471-2164

Abstract

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 theEGFR andPRDM16 genes. Recurrent losses were located at chromosome 12 (q24.13), which includes the genePTPN11 . 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.