PMID- 23706910
OWN - NLM
STAT- MEDLINE
DCOM- 20131119
LR  - 20171116
IS  - 1532-8392 (Electronic)
IS  - 0046-8177 (Linking)
VI  - 44
IP  - 10
DP  - 2013 Oct
TI  - Integrated multimodal genetic testing of Ewing sarcoma--a single-institution 
      experience.
PG  - 2010-9
LID - S0046-8177(13)00114-7 [pii]
LID - 10.1016/j.humpath.2013.03.003 [doi]
AB  - Ewing sarcoma (ES) is an aggressive malignant small round cell tumor that arises 
      in bone or soft tissue of adolescents and young adults. A characteristic 
      molecular finding in ES is EWSR1 gene fusion with ETS (erythroblast 
      transformation-specific) family genes including FLI1 (~90%) and ERG (>5%). Here 
      we report our experience using integrated clinicopathologic, cytogenetic, 
      fluorescence in situ hybridization (FISH), and reverse transcriptase polymerase 
      chain reaction (RT-PCR) analyses of 32 pediatric patients with ES diagnosed in a 
      single institution between 2005 and 2011. Diagnostic EWSR1 rearrangements were 
      detected in 30 (93.8%) of 32 patients. Cytogenetics detected t(11;22) (n = 14) 
      and t(21;22) (n = 1) in 15 (46.9%) patients. FISH detected EWSR1 rearrangements 
      in 27 (96.4%) of 28 patients tested. RT-PCR was positive in 27 (84.4%) of 32 
      patients, including 24 EWSR1-FLI1 and 3 EWSR1-ERG. RT-PCR defined breakpoints and 
      fusion partners in 7 cases with EWSR1 rearrangements detected by FISH. Sanger 
      sequencing further delineated breakpoints in 21 (77.8%) of 27 RT-PCR positive 
      cases. In summary, conventional cytogenetic analysis provided a global view but 
      had a lower detection rate and longer turnaround time than other methods. FISH is 
      a rapid method and theoretically can detect all EWSR1 rearrangements, but it 
      cannot identify all partners and is not completely specific for ES. RT-PCR and 
      sequencing are more sensitive and useful in identifying fusion partners and 
      refining breakpoints; however, these methods can be compromised by poor RNA 
      preservation and primer design. In conclusion, an integrated approach that uses 
      all methods capable of detecting EWSR1 rearrangements has value in the workup of 
      suspected cases of ES.
CI  - Copyright (c) 2013 Elsevier Inc. All rights reserved.
FAU - Warren, Mikako
AU  - Warren M
AD  - Department of Pathology and Immunology, Baylor College of Medicine, Texas 
      Children's Hospital, Houston, TX 77030, USA.
FAU - Weindel, Michael
AU  - Weindel M
FAU - Ringrose, Jo
AU  - Ringrose J
FAU - Venable, Clint
AU  - Venable C
FAU - Reyes, Adriana
AU  - Reyes A
FAU - Terashima, Keita
AU  - Terashima K
FAU - Rao, Pulivarthi
AU  - Rao P
FAU - Chintagumpala, Murali
AU  - Chintagumpala M
FAU - Hicks, M John
AU  - Hicks MJ
FAU - Lopez-Terrada, Dolores
AU  - Lopez-Terrada D
FAU - Lu, Xin-Yan
AU  - Lu XY
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20130522
PL  - United States
TA  - Hum Pathol
JT  - Human pathology
JID - 9421547
RN  - 0 (Calmodulin-Binding Proteins)
RN  - 0 (DNA, Neoplasm)
RN  - 0 (ERG protein, human)
RN  - 0 (EWS-ERG fusion protein, human)
RN  - 0 (EWSR1 protein, human)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (RNA-Binding Protein EWS)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 0 (Transcriptional Regulator ERG)
SB  - IM
MH  - Adolescent
MH  - Bone Neoplasms/*genetics/pathology
MH  - Calmodulin-Binding Proteins/genetics
MH  - Child
MH  - Child, Preschool
MH  - Chromosomes, Human, Pair 11
MH  - Chromosomes, Human, Pair 22
MH  - DNA, Neoplasm/genetics
MH  - Female
MH  - Gene Rearrangement
MH  - Genetic Testing/*methods
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Infant
MH  - Male
MH  - Oncogene Proteins, Fusion/*genetics
MH  - RNA-Binding Protein EWS
MH  - RNA-Binding Proteins/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sarcoma, Ewing/*genetics/secondary
MH  - Soft Tissue Neoplasms/*genetics/pathology
MH  - Trans-Activators/genetics
MH  - Transcription Factors/*genetics
MH  - Transcriptional Regulator ERG
MH  - Translocation, Genetic
MH  - Young Adult
OTO - NOTNLM
OT  - Chromosome analysis
OT  - Ewing sarcoma
OT  - FISH
OT  - Integrated testing
OT  - RT-PCR
OT  - Sequencing
EDAT- 2013/05/28 06:00
MHDA- 2013/11/20 06:00
CRDT- 2013/05/28 06:00
PHST- 2012/12/31 00:00 [received]
PHST- 2013/03/02 00:00 [revised]
PHST- 2013/03/14 00:00 [accepted]
PHST- 2013/05/28 06:00 [entrez]
PHST- 2013/05/28 06:00 [pubmed]
PHST- 2013/11/20 06:00 [medline]
AID - S0046-8177(13)00114-7 [pii]
AID - 10.1016/j.humpath.2013.03.003 [doi]
PST - ppublish
SO  - Hum Pathol. 2013 Oct;44(10):2010-9. doi: 10.1016/j.humpath.2013.03.003. Epub 2013 
      May 22.