PMID- 19773435
OWN - NLM
STAT- MEDLINE
DCOM- 20091203
LR  - 20211020
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 69
IP  - 19
DP  - 2009 Oct 1
TI  - Rearrangements and amplification of IER3 (IEX-1) represent a novel and recurrent 
      molecular abnormality in myelodysplastic syndromes.
PG  - 7518-23
LID - 10.1158/0008-5472.CAN-09-1428 [doi]
AB  - IER3 (formerly IEX-1) encodes a 27-kDa glycoprotein that regulates death 
      receptor-induced apoptosis, interacts with NF-kappaB pathways, and increases 
      expression rapidly in response to cellular stresses such as irradiation. Animal 
      models, gene expression microarray experiments, and functional studies in cell 
      lines have suggested a potential role for IER3 in oncogenesis, but, to date, no 
      abnormalities of IER3 at the DNA level have been reported in patients with 
      neoplasia. Here, we describe breakpoint cloning of a t(6;9)(p21;q34) 
      translocation from a patient with a myelodysplastic syndrome (MDS), facilitated 
      by conversion technology and array-based comparative genomic hybridization, which 
      revealed a rearrangement translocating the IER3 coding region away from critical 
      flanking/regulatory elements and to a transcript-poor chromosomal region, 
      markedly decreasing expression. Using split-signal and locus-specific 
      fluorescence in situ hybridization (FISH) probes, we analyzed 204 patients with 
      diverse hematological malignancies accompanied by clonal chromosome 6p21 
      abnormalities, and found 8 additional patients with MDS with IER3 rearrangements 
      (translocations or amplification). Although FISH studies on 157 additional 
      samples from patients with MDS and a normal-karyotype were unrevealing, and 
      sequencing the IER3 coding and proximal promoter regions of 74 MDS patients 
      disclosed no point mutations, reverse transcription-PCR results suggested that 
      dysregulated expression of IER3 is common in MDS (61% >4-fold increase or 
      decrease in expression with decreased expression primarily in early MDS and 
      increased expression primarily in later MDS progressing toward leukemia), 
      consistent with findings in previous microarray experiments. These data support 
      involvement of IER3 in the pathobiology of MDS.
FAU - Steensma, David P
AU  - Steensma DP
AD  - Mayo Clinic, Rochester, MN 55905, USA. Steensma.david@mayo.edu
FAU - Neiger, Jessemy D
AU  - Neiger JD
FAU - Porcher, Julie C
AU  - Porcher JC
FAU - Keats, J Jonathan
AU  - Keats JJ
FAU - Bergsagel, P Leif
AU  - Bergsagel PL
FAU - Dennis, Thomas R
AU  - Dennis TR
FAU - Knudson, Ryan A
AU  - Knudson RA
FAU - Jenkins, Robert B
AU  - Jenkins RB
FAU - Santana-Davila, Rafael
AU  - Santana-Davila R
FAU - Kumar, Rajiv
AU  - Kumar R
FAU - Ketterling, Rhett P
AU  - Ketterling RP
LA  - eng
GR  - P50 CA100707-09/CA/NCI NIH HHS/United States
GR  - K12 CA090628-07/CA/NCI NIH HHS/United States
GR  - R21 DK077669/DK/NIDDK NIH HHS/United States
GR  - K12 CA90628/CA/NCI NIH HHS/United States
GR  - K12 CA090628/CA/NCI NIH HHS/United States
GR  - 2 P50 CA100707-067285/CA/NCI NIH HHS/United States
GR  - R01 DK076829/DK/NIDDK NIH HHS/United States
GR  - P50 CA100707/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20090922
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (IER3 protein, human)
RN  - 0 (Membrane Proteins)
SB  - IM
MH  - Aged
MH  - Animals
MH  - Apoptosis Regulatory Proteins/*genetics
MH  - Base Sequence
MH  - Chromosomes, Human, Pair 6
MH  - Chromosomes, Human, Pair 9
MH  - Comparative Genomic Hybridization
MH  - Gene Amplification
MH  - Gene Rearrangement
MH  - Hematopoietic Stem Cells/cytology
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Membrane Proteins/*genetics
MH  - Mice
MH  - Molecular Sequence Data
MH  - Myelodysplastic Syndromes/*genetics
MH  - Point Mutation
MH  - Polymorphism, Genetic
MH  - Reverse Transcriptase Polymerase Chain Reaction
PMC - PMC3157243
MID - NIHMS140265
EDAT- 2009/09/24 06:00
MHDA- 2009/12/16 06:00
PMCR- 2011/08/17
CRDT- 2009/09/24 06:00
PHST- 2009/09/24 06:00 [entrez]
PHST- 2009/09/24 06:00 [pubmed]
PHST- 2009/12/16 06:00 [medline]
PHST- 2011/08/17 00:00 [pmc-release]
AID - 0008-5472.CAN-09-1428 [pii]
AID - 10.1158/0008-5472.CAN-09-1428 [doi]
PST - ppublish
SO  - Cancer Res. 2009 Oct 1;69(19):7518-23. doi: 10.1158/0008-5472.CAN-09-1428. Epub 
      2009 Sep 22.