PMID- 24798186
OWN - NLM
STAT- MEDLINE
DCOM- 20150709
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 5
DP  - 2014
TI  - Comparison between karyotyping-FISH-reverse transcription PCR and 
      RNA-sequencing-fusion gene identification programs in the detection of 
      KAT6A-CREBBP in acute myeloid leukemia.
PG  - e96570
LID - 10.1371/journal.pone.0096570 [doi]
LID - e96570
AB  - An acute myeloid leukemia was suspected of having a t(8;16)(p11;p13) resulting in 
      a KAT6A-CREBBP fusion because the bone marrow was packed with monoblasts showing 
      marked erythrophagocytosis. The diagnostic karyotype was 
      46,XY,add(1)(p13),t(8;21)(p11;q22),der(16)t(1;16)(p13;p13)[9]/46,XY[1]; thus, no 
      direct confirmation of the suspicion could be given although both 8p11 and 16p13 
      seemed to be rearranged. The leukemic cells were examined in two ways to find out 
      whether a cryptic KAT6A-CREBBP was present. The first was the "conventional" 
      approach: G-banding was followed by fluorescence in situ hybridization (FISH) and 
      reverse transcription PCR (RT-PCR). The second was RNA-Seq followed by data 
      analysis using FusionMap and FusionFinder programs with special emphasis on 
      candidates located in the 1p13, 8p11, 16p13, and 21q22 breakpoints. FISH analysis 
      indicated the presence of a KAT6A/CREBBP chimera. RT-PCR followed by Sanger 
      sequencing of the amplified product showed that a chimeric KAT6A-CREBBP 
      transcript was present in the patients bone marrow. Surprisingly, however, 
      KATA6A-CREBBP was not among the 874 and 35 fusion transcripts identified by the 
      FusionMap and FusionFinder programs, respectively, although 11 sequences of the 
      raw RNA-sequencing data were KATA6A-CREBBP fragments. This illustrates that 
      although many fusion transcripts can be found by RNA-Seq combined with FusionMap 
      and FusionFinder, the pathogenetically essential fusion is not always picked up 
      by the bioinformatic algorithms behind these programs. The present study not only 
      illustrates potential pitfalls of current data analysis programs of whole 
      transcriptome sequences which make them less useful as stand-alone techniques, 
      but also that leukemia diagnosis still relies on integration of clinical, 
      hematologic, and genetic disease features of which the former two by no means 
      have become superfluous.
FAU - Panagopoulos, Ioannis
AU  - Panagopoulos I
AD  - Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, 
      The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; Centre for 
      Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
FAU - Torkildsen, Synne
AU  - Torkildsen S
AD  - Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, 
      The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; Centre for 
      Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway; 
      Department of Hematology, Oslo University Hospital, Oslo, Norway.
FAU - Gorunova, Ludmila
AU  - Gorunova L
AD  - Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, 
      The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; Centre for 
      Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
FAU - Tierens, Anne
AU  - Tierens A
AD  - Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, 
      Oslo, Norway.
FAU - Tjonnfjord, Geir E
AU  - Tjonnfjord GE
AD  - Department of Hematology, Oslo University Hospital, Oslo, Norway; Faculty of 
      Medicine, University of Oslo, Oslo, Norway.
FAU - Heim, Sverre
AU  - Heim S
AD  - Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, 
      The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; Centre for 
      Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway; 
      Faculty of Medicine, University of Oslo, Oslo, Norway.
LA  - eng
PT  - Case Reports
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140505
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Oncogene Proteins, Fusion)
RN  - EC 2.3.1.48 (CREB-Binding Protein)
RN  - EC 2.3.1.48 (CREBBP protein, human)
RN  - EC 2.3.1.48 (Histone Acetyltransferases)
RN  - EC 2.3.1.48 (KAT6A protein, human)
SB  - IM
MH  - Adult
MH  - CREB-Binding Protein/*genetics
MH  - Histone Acetyltransferases/*genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Karyotyping
MH  - Leukemia, Myeloid, Acute/*genetics
MH  - Male
MH  - Oncogene Proteins, Fusion/*genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sequence Analysis, RNA
MH  - Translocation, Genetic
PMC - PMC4010518
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/05/07 06:00
MHDA- 2015/07/15 06:00
PMCR- 2014/05/05
CRDT- 2014/05/07 06:00
PHST- 2014/02/20 00:00 [received]
PHST- 2014/04/09 00:00 [accepted]
PHST- 2014/05/07 06:00 [entrez]
PHST- 2014/05/07 06:00 [pubmed]
PHST- 2015/07/15 06:00 [medline]
PHST- 2014/05/05 00:00 [pmc-release]
AID - PONE-D-14-06530 [pii]
AID - 10.1371/journal.pone.0096570 [doi]
PST - epublish
SO  - PLoS One. 2014 May 5;9(5):e96570. doi: 10.1371/journal.pone.0096570. eCollection 
      2014.