title: MiRNA-9 and MiRNA-200a distinguish hemangioblastomas from metastatic clear cell renal cell carcinomas in the CNS.
abstract: Central nervous system (CNS) tumors in von Hippel-Lindau syndrome (VHL) include hemangioblastomas and metastatic clear cell renal cell carcinomas (Met CCRCC). While these tumors often show similar histologic features, differentiating them is of significant importance as Met CCRCC are higher-grade tumors with worse prognosis. No single current immunohistochemical marker unequivocally differentiates between these two entities. MicroRNAs (miRNAs) are noncoding cellular small RNA molecules that play an important role in cancer. We hypothesized that hemangioblastomas and Met CCRCC display distinct miRNA signatures enabling their histologic differentiation. MiRNAs were profiled in 10 cases each of hemangioblastomas, Met CCRCC and primary CCRCC. Ten miRNAs had greater abundance (including miR-9 (∼10-fold) and miR-135a (∼7-fold)) and 39 miRNAs were lower [including miR-200a (∼22-fold) and miR-200b (∼12-fold)] in hemangioblastomas compared with Met CCRCC. Quantitative real-time RT-PCR in 20 hemangioblastomas and 13 Met CCRCC showed a 12-fold increase in miR-9 and a 15-fold decrease of miR-200a in hemangioblastomas compared with Met CCRCC. Finally, in situ hybridization for miR-9 in 15 hemangioblastomas and 10 Met CCRCC confirmed these results. Our data suggest that miR-9 and miR-200a can distinguish between hemangioblastomas and Met CCRCC. Further, these results may also provide insight in understanding the biology of hemangioblastomas.
authors.affiliation: Division of Neuropathology, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA. vennetis@mskcc.org
authors.forename: Sriram
authors.initials: S
authors.lastname: Venneti
authors.forename: LaTasha A
authors.initials: LA
authors.lastname: Boateng
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Friedman
authors.forename: Donald A
authors.initials: DA
authors.lastname: Baldwin
authors.forename: John W
authors.initials: JW
authors.lastname: Tobias
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Judkins
authors.forename: Zissimos
authors.initials: Z
authors.lastname: Mourelatos
authors.forename: Priti
authors.initials: P
authors.lastname: Lal
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000175:diagnosis* / Q000235:genetics / Q000556:secondary; D005260:Female; D018325:Hemangioblastoma / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D006801:Humans; D017403:In Situ Hybridization; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D008297:Male; D035683:MicroRNAs; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult; D006623:von Hippel-Lindau Disease / Q000150:complications
chemical_list: D014408:Biomarkers, Tumor; C533896:MIRN200 microRNA, human; C541874:MIRN92 microRNA, human; D035683:MicroRNAs
references.citation: Mod Pathol. 1989 Nov;2(6):638-51
references.pmid: 2479946
references.citation: Lancet. 2003 Jun 14;361(9374):2059-67
references.pmid: 12814730
references.citation: J Neurosci. 2011 Mar 2;31(9):3407-22
references.pmid: 21368052
references.citation: Histopathology. 2008 May;52(6):674-81
references.pmid: 18393979
references.citation: J Neurosci. 2011 Jan 19;31(3):809-18
references.pmid: 21248104
references.citation: JAMA. 2008 Sep 17;300(11):1334-42
references.pmid: 18799446
references.citation: Mol Cancer. 2008 Apr 28;7:35
references.pmid: 18442408
references.citation: Am J Surg Pathol. 2008 Jul;32(7):1051-9
references.pmid: 18496143
references.citation: Nature. 2005 Jun 9;435(7043):834-8
references.pmid: 15944708
references.citation: Nat Neurosci. 2008 Jun;11(6):641-8
references.pmid: 18454145
references.citation: Nat Protoc. 2010 Jun;5(6):1061-73
references.pmid: 20539282
references.citation: Nature. 2011 Jul 13;476(7359):228-31
references.pmid: 21753754
references.citation: Clin Neuropathol. 2000 May-Jun;19(3):131-7
references.pmid: 14606586
references.citation: J Neurosci. 2008 Dec 31;28(53):14341-6
references.pmid: 19118166
references.citation: Cancer Res. 2009 Jul 15;69(14):5936-45
references.pmid: 19549897
references.citation: RNA. 2006 Feb;12(2):187-91
references.pmid: 16373485
references.citation: Brain Pathol. 2009 Jul;19(3):375-83
references.pmid: 18624795
references.citation: Am J Surg Pathol. 2003 Aug;27(8):1152-6
references.pmid: 12883249
references.citation: Am J Surg Pathol. 2011 Feb;35(2):262-7
references.pmid: 21263247
references.citation: Nat Struct Mol Biol. 2009 Apr;16(4):365-71
references.pmid: 19330006
references.citation: Cancer Res. 1999 May 1;59(9):2251-3
references.pmid: 10232616
references.citation: Oncogene. 2010 Oct 21;29(42):5724-8
references.pmid: 20676129
references.citation: Mod Pathol. 2005 Jun;18(6):788-94
references.pmid: 15578072
references.citation: Neurosci Lett. 2006 Jan 16;392(3):178-80
references.pmid: 16300893
references.citation: J Neurooncol. 2006 Dec;80(3):219-25
references.pmid: 17077939
references.citation: PLoS Med. 2007 Feb;4(2):e60
references.pmid: 17298169
references.citation: Neuropathology. 2010 Dec;30(6):580-5
references.pmid: 20374497
references.citation: J Exp Clin Cancer Res. 2009 Jun 16;28:82
references.pmid: 19531230
references.citation: Nat Cell Biol. 2010 Mar;12(3):247-56
references.pmid: 20173740
references.citation: Mol Cancer. 2010 Jan 26;9:16
references.pmid: 20102618
references.citation: Acta Neuropathol. 2005 May;109(5):497-502
references.pmid: 15864611
references.citation: BMC Med. 2010 Oct 21;8:64
references.pmid: 20964835
references.citation: Nat Rev Cancer. 2006 Nov;6(11):857-66
references.pmid: 17060945
references.citation: Adv Anat Pathol. 2010 Mar;17(2):150-3
references.pmid: 20179436
references.citation: Cell Stem Cell. 2010 Apr 2;6(4):323-35
references.pmid: 20362537
references.citation: J Neuropathol Exp Neurol. 1997 Dec;56(12):1349-55
references.pmid: 9413283
references.citation: FEBS J. 2009 Oct;276(19):5537-46
references.pmid: 19702828