title: The High Expression of the microRNA 17-92 Cluster and its Paralogs, and the Downregulation of the Target Gene PTEN, Is Associated with Primary Cutaneous B-Cell Lymphoma Progression.
abstract: The oncogenic microRNA (miR) 17-92 cluster has a causative role in the lymphomagenesis of nodal B-cell lymphomas, by activating proliferation and inhibiting apoptosis. Here we analyzed primary cutaneous B-cell lymphomas for the miR-17-92 cluster and its paralogs miR-106a-363 and miR-106b-25. In 22 primary cutaneous diffuse large B-cell lymphomas, leg type (PCLBCL-LT) compared with 22 primary cutaneous follicle center lymphomas (PCFCLs), we found that miR-20a and miR-106a were overexpressed. Multivariate Cox analysis showed that higher miR-20a and miR-20b expression levels were associated with shorter disease-free and overall survival, independently from histological type. Gene expression profiling also showed a downregulation of 8 candidate target genes of miR-20a, miR-20b, and miR-106a in PCLBCL-LT compared with PCFCL. Among the candidate target genes, PTEN, NCOA3, and CAPRIN2 were confirmed to be underexpressed in PCLBCL-LT using quantitative reverse transcriptase-PCR on CD20-positive laser-microdissected tumor cells. In multivariate Cox analysis, lower PTEN mRNA expression level was associated with shorter disease-free survival (DFS), independently from the histological type. Altogether, this molecular and bioinformatic study of 44 patient skin biopsy samples showed that the oncogenic miR-17-92 cluster and its paralogs were involved in cutaneous B-cell lymphoma progression, and that the downregulation of the target gene PTEN was associated with shorter DFS.
authors: Inserm U1165, Institut Universitaire d'Hématologie, Hôpital Saint Louis, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Laboratoire de Pathologie, UMR-S 1165, Paris, France; AP-HP, Hôpital Saint-Louis, Department of Pathology, Paris, France. Electronic address: maxime.battistella@sls.aphp.fr.
authors: Maxime
authors: M
authors: Battistella
authors: Inserm U1165, Institut Universitaire d'Hématologie, Hôpital Saint Louis, Paris, France; Department of Pathology, Hospital Universitario Fundacion Santa Fe de Bogota, Bogota, Colombia.
authors: Martha
authors: M
authors: Romero
authors: INSERM, UMR970, Paris-Cardiovascular Research Center, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, France.
authors: Luis-Jaime
authors: LJ
authors: Castro-Vega
authors: Inserm U1165, Institut Universitaire d'Hématologie, Hôpital Saint Louis, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Laboratoire de Pathologie, UMR-S 1165, Paris, France.
authors: Guillaume
authors: G
authors: Gapihan
authors: Inserm U1165, Institut Universitaire d'Hématologie, Hôpital Saint Louis, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Laboratoire de Pathologie, UMR-S 1165, Paris, France; AP-HP, Hôpital Saint-Louis, Department of Pathology, Paris, France.
authors: Fatiha
authors: F
authors: Bouhidel
authors: AP-HP, Hôpital Saint-Louis, Department of Dermatology, Paris, France; Inserm, U 976, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Faculté de Médecine, Paris, France.
authors: Martine
authors: M
authors: Bagot
authors: INSERM, IAME, UMR 1137, Université Paris Diderot, Paris, France.
authors: Jean-Paul
authors: JP
authors: Feugeas
authors: Inserm U1165, Institut Universitaire d'Hématologie, Hôpital Saint Louis, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Laboratoire de Pathologie, UMR-S 1165, Paris, France; AP-HP, Hôpital Saint-Louis, Department of Pathology, Paris, France.
authors: Anne
authors: A
authors: Janin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018951:Antigens, CD20 / Q000378:metabolism; D017209:Apoptosis; D001706:Biopsy; D019295:Computational Biology; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D005810:Multigene Family; D015999:Multivariate Analysis; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D016016:Proportional Hazards Models; D062085:RNA, Long Noncoding; D012333:RNA, Messenger / Q000378:metabolism; D012867:Skin / Q000378:metabolism / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics*
chemical_list: D018951:Antigens, CD20; C568997:MIR17HG, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
references: Blood. 2007 Jul 15;110(2):479-84
references: 17339420
references: Nat Rev Mol Cell Biol. 2012 Apr 04;13(5):283-96
references: 22473468
references: J Clin Oncol. 2001 Aug 15;19(16):3602-10
references: 11504742
references: Curr Opin Hematol. 2011 Jul;18(4):266-72
references: 21519241
references: EMBO J. 2012 May 2;31(9):2207-21
references: 22473208
references: Nat Immunol. 2008 Sep;9(9):1065-73
references: 18677316
references: Blood. 2005 May 1;105(9):3671-8
references: 15308563
references: Blood. 2005 May 15;105(10):3768-85
references: 15692063
references: Nature. 2005 Jun 9;435(7043):828-33
references: 15944707
references: Nat Rev Genet. 2012 Mar 13;13(4):227-32
references: 22411467
references: PLoS One. 2011;6(6):e20781
references: 21698185
references: Radiat Oncol. 2010 Nov 01;5:100
references: 21040528
references: Leukemia. 2012 May;26(5):1064-72
references: 22116552
references: Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2257-61
references: 16461460
references: Proc Natl Acad Sci U S A. 2013 Jul 23;110(30):12420-5
references: 23840064
references: Cancer Res. 2009 Sep 1;69(17):7071-8
references: 19690137
references: PLoS One. 2011 Jan 20;6(1):e16138
references: 21283765
references: EMBO J. 2013 Aug 28;32(17):2377-91
references: 23921550
references: Am J Pathol. 2014 Oct;184(10 ):2828-39
references: 25239565
references: JAMA Dermatol. 2014 May;150(5):535-41
references: 24647650
references: Genome Res. 2009 Jan;19(1):92-105
references: 18955434
references: Mol Cell Neurosci. 2004 Apr;25(4):692-706
references: 15080897
references: Blood. 2005 Oct 1;106(7):2491-7
references: 15947086
references: Blood. 2009 Jan 8;113(2):396-402
references: 18941111
references: Br J Dermatol. 2007 Dec;157(6):1205-11
references: 17941944
references: Exp Hematol. 2005 Mar;33(3):344-52
references: 15730858
references: Nature. 2008 Sep 4;455(7209):64-71
references: 18668037
references: Mod Pathol. 2013 Feb;26(2):171-81
references: 22936066
references: Cancer Res. 2002 Nov 1;62(21):6178-86
references: 12414645
references: Arch Dermatol. 2007 Sep;143(9):1144-50
references: 17875875
references: Proc Natl Acad Sci U S A. 2008 Sep 9;105(36):13520-5
references: 18765795
references: Clin Lymphoma Myeloma Leuk. 2014 Oct;14(5):335-42
references: 24650973
references: Cell Host Microbe. 2011 Nov 17;10(5):515-26
references: 22100165
references: Nat Immunol. 2008 Apr;9(4):405-14
references: 18327259
references: Leuk Lymphoma. 2010 Sep;51(9):1692-8
references: 20807096
references: PLoS One. 2013 Dec 16;8(12):e82471
references: 24358187
references: Lancet Oncol. 2013 Dec;14(13):1295-306
references: 24239208
references: Blood. 2008 Sep 1;112(5):1600-9
references: 18567836
references: Cell Death Differ. 2013 Dec;20(12):1603-14
references: 24212931
references: Leukemia. 2013 Jan;27(1):16-23
references: 22836911
references: Histopathology. 2011 Jan;58(1):39-48
references: 21261682
references: Genome Res. 2010 May;20(5):589-99
references: 20439436
references: Lab Invest. 2012 Nov;92(11):1574-82
references: 22964854
references: J Clin Oncol. 2007 Apr 20;25(12):1581-7
references: 17353548
references: J Cutan Pathol. 2005 Nov;32(10):647-74
references: 16293178
references: JAMA Dermatol. 2014 Nov;150(11):1173-9
references: 25055137
references: Cancer Res. 2012 Nov 1;72(21):5463-72
references: 22915757
references: J Clin Oncol. 2005 May 20;23(15):3390-5
references: 15908651
references: Clin Cancer Res. 2011 Jun 15;17(12):4125-35
references: 21525173
references: Cell. 2008 Mar 7;132(5):875-86
references: 18329372
references: Cell. 2008 Apr 18;133(2):217-22
references: 18423194
references: Proc Natl Acad Sci U S A. 2009 Sep 15;106(37):15732-7
references: 19706389