PMID- 31237044
OWN - NLM
STAT- MEDLINE
DCOM- 20200128
LR  - 20221207
IS  - 1098-2744 (Electronic)
IS  - 0899-1987 (Linking)
VI  - 58
IP  - 10
DP  - 2019 Oct
TI  - Aberrant ERG expression associates with downregulation of miR-4638-5p and 
      selected genomic alterations in a subset of diffuse large B-cell lymphoma.
PG  - 1846-1854
LID - 10.1002/mc.23074 [doi]
AB  - ERG (avian v-ets erythroblastosis virus E26 oncogene homolog), an oncoprotein in 
      prostate carcinoma and Ewing's sarcoma is associated with poor prognosis in 
      patients with acute myeloid leukemia and T lymphoblastic leukemia. However little 
      is known about ERG in lymphoma. Here we studied ERG in diffuse large B-cell 
      lymphoma (DLBCL) by immunohistochemistry, fluorescence in situ hybridization 
      (FISH), genome-wide microRNA (miRNA) expression profiling, real-time 
      reverse-transcriptase polymerase chain reaction (RT-PCR) and whole exome 
      sequencing (WES). Approximately 30% of de novo DLBCLs (37 of 118) expressed ERG 
      (ERG+). ERG expression showed no significant correlation with DLBCL 
      cell-of-origin classification, patient's age, sex, nodal, or extranodal disease 
      status, tumor expression of p53 or p63. There was no ERG rearrangement in 10 
      randomly selected ERG+ DLBCLs by FISH. Forty-three miRNAs showed significant 
      differential expression between ERG+ and ERG- DLBCLs. Downregulation of 
      miR-4638-5p was confirmed by real-time RT-PCR. WES not only confirmed known gene 
      mutations in DLBCLs but also revealed multiple novel gene mutations in POLA1, 
      E2F1, PSMD8, AXIN1, GAB2, and GNB2L1, which occur more frequently in ERG+ DLBCLs. 
      In conclusion, our studies demonstrated aberrant ERG expression in a subset of 
      DLBCL, which is associated with downregulation of miR-4638-5p. In comparison with 
      ERG-negative DLBCL, ERG+ DLBCL more likely harbors mutations in genes important 
      in cell cycle control, B-cell receptor-mediated signaling and degradation of 
      beta-catenin. Further clinicopathological correlation and functional studies of 
      ERG-related miRNAs and pathways may provide new insight into the pathogenesis of 
      DLBCL and reveal novel targets for better management of patients with DLBCL.
CI  - (c) 2019 Wiley Periodicals, Inc.
FAU - Zhang, Shanxiang
AU  - Zhang S
AUID- ORCID: 0000-0001-8525-7021
AD  - Department of Pathology & Laboratory Medicine, Indiana University School of 
      Medicine, Indianapolis, Indiana.
FAU - Wang, Lin
AU  - Wang L
AD  - Department of Pathology & Laboratory Medicine, Indiana University School of 
      Medicine, Indianapolis, Indiana.
FAU - Cheng, Liang
AU  - Cheng L
AD  - Department of Pathology & Laboratory Medicine, Indiana University School of 
      Medicine, Indianapolis, Indiana.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190624
PL  - United States
TA  - Mol Carcinog
JT  - Molecular carcinogenesis
JID - 8811105
RN  - 0 (ERG protein, human)
RN  - 0 (MIRN4638 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Transcriptional Regulator ERG)
SB  - IM
MH  - Disease-Free Survival
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Genomics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Lymphoma, Large B-Cell, Diffuse/*genetics/pathology
MH  - Male
MH  - MicroRNAs/*genetics
MH  - Middle Aged
MH  - Neoplasm Proteins/genetics
MH  - Prognosis
MH  - Signal Transduction/genetics
MH  - Transcriptional Regulator ERG/genetics
MH  - Exome Sequencing
OTO - NOTNLM
OT  - ERG
OT  - diffuse large B-cell lymphoma
OT  - genomic pathway
OT  - microRNA
OT  - whole exome sequencing
EDAT- 2019/06/27 06:00
MHDA- 2020/01/29 06:00
CRDT- 2019/06/26 06:00
PHST- 2019/03/27 00:00 [received]
PHST- 2019/05/22 00:00 [revised]
PHST- 2019/05/31 00:00 [accepted]
PHST- 2019/06/27 06:00 [pubmed]
PHST- 2020/01/29 06:00 [medline]
PHST- 2019/06/26 06:00 [entrez]
AID - 10.1002/mc.23074 [doi]
PST - ppublish
SO  - Mol Carcinog. 2019 Oct;58(10):1846-1854. doi: 10.1002/mc.23074. Epub 2019 Jun 24.