RRC ID 12189
Author Yagasaki F, Jinnai I, Yoshida S, Yokoyama Y, Matsuda A, Kusumoto S, Kobayashi H, Terasaki H, Ohyashiki K, Asou N, Murohashi I, Bessho M, Hirashima K.
Title Fusion of TEL/ETV6 to a novel ACS2 in myelodysplastic syndrome and acute myelogenous leukemia with t(5;12)(q31;p13).
Journal Genes Chromosomes Cancer
Abstract We identified a novel human long fatty acyl CoA synthetase 2 gene, ACS2, as a new ETV6 fusion partner gene in a recurrent t(5;12)(q31;p13) translocation in a patient with refractory anemia with excess blasts (RAEB) with basophilia, a patient with acute myelogenous leukemia (AML) with eosinophilia, and a patient with acute eosinophilic leukemia (AEL). ACS2 is expressed in the brain and bone marrow and is highly conserved in man and rats. The resulting ETV6/ACS2 fusion transcripts showed an out-frame fusion of exon 1 of ETV6 to exon 1 of ACS2 in the AEL case, an out-frame fusion of exon 1 of ETV6 to exon 11 of ACS2 in the AML case, and a short in-frame fusion of ETV6 exon 1 to the 3' untranslated region of ACS2 in the RAEB case. Reciprocal ACS2/ETV6 transcripts were identified in two of the cases. Fluorescence in situ hybridization (FISH) analysis with ETV6 cosmids on 12p13, and BACs and P1s on 5q31, demonstrated that the 5q31 breakpoints of the AML and AEL cases involved the 5' portion of the ACS2 gene, and that the 5q31, breakpoint of the RAEB case involved the 3' portion of the ACS2 gene. None of the resulting chimeric transcripts except for the ACS2/ETV6 transcript in the RAEB case led to a fusion protein. Disruption of the second ETV6 allele by t(12;19) was detected in the AML case by FISH analysis. These observations suggest that the disruption of ETV6 and/or ACS2 may lead to the pathogenesis of hematologic malignancies with t(5;12)(q31;p13).
Volume 26(3)
Pages 192-202
Published 1999-11-1
DOI 10.1002/(sici)1098-2264(199911)26:3<192::aid-gcc2>3.0.co;2-e
PII 10.1002/(SICI)1098-2264(199911)26:3<192::AID-GCC2>3.0.CO;2-E
PMID 10502316
MeSH Adult Amino Acid Sequence Artificial Gene Fusion Base Sequence Blotting, Northern Chromosome Mapping Chromosomes, Human, Pair 12* Chromosomes, Human, Pair 5* Coenzyme A Ligases / genetics* DNA, Neoplasm / analysis DNA-Binding Proteins / genetics* Exons Female Humans In Situ Hybridization, Fluorescence Leukemia, Myeloid, Acute / genetics* Male Middle Aged Molecular Sequence Data Nuclear Proteins / genetics Phosphoproteins / genetics Proto-Oncogene Proteins c-ets RNA, Neoplasm / analysis Repressor Proteins* Reverse Transcriptase Polymerase Chain Reaction Sequence Analysis, DNA Transcription Factors / genetics* Translocation, Genetic*
IF 3.444
Times Cited 68
DNA material CEPH MEGA YAC clone 964-C-10 745-F-8 880-G-9 638-E-12.