Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Strehl, S; Nebral, K; König, M; Harbott, J; Strobl, H; Ratei, R; Struski, S; Bielorai, B; Lessard, M; Zimmermann, M; Haas, OA; Izraeli, S.
ETV6-NCOA2: a novel fusion gene in acute leukemia associated with coexpression of T-lymphoid and myeloid markers and frequent NOTCH1 mutations.
Clin Cancer Res. 2008; 14(4):977-983
Doi: 10.1158/1078-0432.CCR-07-4022
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
Google Scholar
- Co-Autor*innen der Med Uni Graz
- Strobl Herbert
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- Purpose: The ETV6 gene has been reported to be fused to a multitude of partner genes in various hematologic malignancies with 12p13 aberrations. Cytogenetic analysis of six cases of childhood acute lymphoblastic leukemia revealed a novel recurrent t(8;12) (q13;p13), suggesting involvement of ETV6. Experimental Design: Fluorescence in situ hybridization was used to confirm the involvement of ETV6 in the t(8;12)(q13;p13) and reverse transcription-PCR was used to identify the ETV6 partner gene. Detailed immunologic characterization was done, and owing to their lineage promiscuity, the leukemic blast cells were analyzed for NOTCH1 mutations. Results: We have identified a novel recurrent t(8;12)(q13;p13), which results in a fusion between the transcriptional repressor ETV6 (TEL) and the transcriptional coactivator NCOA2 (TIF2) in six cases of childhood leukemia expressing both T-lymphoid and myeloid antigens. The ETV6-NCOA2 transcript encodes a chimeric protein that consists of the pointed protein interaction motif of ETV6 that is fused to the COOH terminus of NCOA2, including the cyclic AMP - responsive element binding protein - binding protein (CBP) interaction and the AD2 activation domains. The absence of the reciprocal NCOA2-ETV6 transcript in one of the cases suggests that the ETV6-NCOA2 chimeric protein and not the reciprocal NCOA2-ETV6 is responsible for leukemogenesis. In addition, ETV6-NCOA2 leukemia shows a high frequency of heterozygous activating NOTCH1 mutations, which disrupt the heterodimerization or the PESTdomains. Conclusions: The ETV6-NCOA2 fusion may define a novel subgroup of acute leukemia with T-lymphoid and myeloid features, which is associated with a high prevalence of NOTCH1 mutations.
- Find related publications in this database (using NLM MeSH Indexing)
- Adolescent -
- Amino Acid Sequence -
- Base Sequence -
- Child -
- Child, Preschool -
- Female -
- Humans -
- Immunophenotyping -
- In Situ Hybridization, Fluorescence -
- Male -
- Molecular Sequence Data -
- Mutation -
- Nuclear Receptor Coactivator 2 - genetics
- Oncogene Fusion - genetics
- Oncogene Proteins, Fusion - genetics
- Precursor Cell Lymphoblastic Leukemia-Lymphoma - classification Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics
- Proto-Oncogene Proteins c-ets - genetics
- Receptor, Notch1 - genetics
- Repressor Proteins - genetics
- Reverse Transcriptase Polymerase Chain Reaction -