TY - JOUR
T1 - Identification of genomic aberrations in hemangioblastoma by droplet digital PCR and SNP microarray highlights novel candidate genes and pathways for pathogenesis
AU - Mehrian-Shai, Ruty
AU - Yalon, Michal
AU - Moshe, Itai
AU - Barshack, Iris
AU - Nass, Dvorah
AU - Jacob, Jasmine
AU - Dor, Chen
AU - Reichardt, Juergen K.V.
AU - Constantini, Shlomi
AU - Toren, Amos
N1 - Publisher Copyright:
© 2016 Mehrian-Shai et al.
PY - 2016/1/14
Y1 - 2016/1/14
N2 - 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.
AB - 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.
KW - CGH
KW - Cancer
KW - Digital PCR
KW - Hemangioblastoma
UR - http://www.scopus.com/inward/record.url?scp=84954181330&partnerID=8YFLogxK
U2 - 10.1186/s12864-016-2370-6
DO - 10.1186/s12864-016-2370-6
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C2 - 26768750
AN - SCOPUS:84954181330
SN - 1471-2164
VL - 17
JO - BMC Genomics
JF - BMC Genomics
IS - 1
M1 - 56
ER -