PMID- 29299133
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 8
IP  - 66
DP  - 2017 Dec 15
TI  - Domain retention in transcription factor fusion genes and its biological and 
      clinical implications: a pan-cancer study.
PG  - 110103-110117
LID - 10.18632/oncotarget.22653 [doi]
AB  - Genomic rearrangements involving transcription factors (TFs) can form fusion 
      proteins resulting in either enhanced, weakened, or even loss of TF activity. 
      Functional domain (FD) retention is a critical factor in the activity of 
      transcription factor fusion genes (TFFGs). A systematic investigation of FD 
      retention in TFFGs and their outcome (e.g. expression changes) in a pan-cancer 
      study has not yet been completed. Here, we examined the FD retention status in 
      386 TFFGs across 13 major cancer types and identified 83 TFFGs involving 67 TFs 
      that retained FDs. To measure the potential biological relevance of TFs in TFFGs, 
      we introduced a Major Active Isofusion Index (MAII) and built a prioritized TFFG 
      network using MAII scores and the observed frequency of fusion positive samples. 
      Interestingly, the four TFFGs (PML-RARA, RUNX1-RUNX1T1, TMPRSS2-ERG, and 
      SFPQ-TFE3) with the highest MAII scores showed 50 differentially expressed target 
      genes (DETGs) in fusion-positive versus fusion-negative cancer samples. DETG 
      analysis revealed that they were involved in tumorigenesis-related processes in 
      each cancer type. PLAU, which encodes plasminogen activator urokinase and serves 
      as a biomarker for tumor invasion, was found to be consistently activated in the 
      samples with the highest MAII scores. Among the 50 DETGs, 21 were drug targetable 
      genes. Fourteen of these 21 DETGs were expressed in acute myeloid leukemia (AML) 
      samples. Accordingly, we constructed an AML-specific TFFG network, which included 
      38 DETGs in RUNX1-RUNX1T1 or PML-RARA positive samples. In summary, this study 
      revealed several TFFGs and their potential target genes, and provided insights 
      into the clinical implications of TFFGs.
FAU - Kim, Pora
AU  - Kim P
AD  - Center for Precision Health, School of Biomedical Informatics, The University of 
      Texas Health Science Center at Houston, Houston, TX 77030, USA.
FAU - Ballester, Leomar Y
AU  - Ballester LY
AD  - Department of Pathology and Laboratory Medicine, The University of Texas Health 
      Science Center at Houston, Houston, TX 77030, USA.
FAU - Zhao, Zhongming
AU  - Zhao Z
AD  - Center for Precision Health, School of Biomedical Informatics, The University of 
      Texas Health Science Center at Houston, Houston, TX 77030, USA.
AD  - Human Genetics Center, School of Public Health, The University of Texas Health 
      Science Center at Houston, Houston, TX 77030, USA.
LA  - eng
GR  - R01 LM012806/LM/NLM NIH HHS/United States
PT  - Journal Article
DEP - 20171124
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
PMC - PMC5746368
OTO - NOTNLM
OT  - PML-RARA
OT  - differential expression
OT  - functional domain retention
OT  - gene fusion network
OT  - transcription factor fusion gene
COIS- CONFLICTS OF INTEREST The authors declare no conflicts of interest.
EDAT- 2018/01/05 06:00
MHDA- 2018/01/05 06:01
PMCR- 2017/12/15
CRDT- 2018/01/05 06:00
PHST- 2017/07/18 00:00 [received]
PHST- 2017/10/25 00:00 [accepted]
PHST- 2018/01/05 06:00 [entrez]
PHST- 2018/01/05 06:00 [pubmed]
PHST- 2018/01/05 06:01 [medline]
PHST- 2017/12/15 00:00 [pmc-release]
AID - 22653 [pii]
AID - 10.18632/oncotarget.22653 [doi]
PST - epublish
SO  - Oncotarget. 2017 Nov 24;8(66):110103-110117. doi: 10.18632/oncotarget.22653. 
      eCollection 2017 Dec 15.