ETV6-NCOA2: A Novel Fusion Gene in Acute Leukemia Associated

Abstract Purpose:TheETV6 genehas been reported tobe fused to amultitude of partner genes invarious hematologic malignancies with12p13 aberrations. Cytogenetic analysis of six cases of childhood acute lymphoblastic leukemia revealed anovel 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 forNOTCH1mutations. Results:We have identified a novel recurrent t(8;12)(q13;p13), which results in a fusion be-tween the transcriptional repressor ETV6 (TEL) and the transcriptional coactivator NCOA2 (TIF2) in six cases of childhood leukemia expressing both T-lymphoid and myeloid anti-gens. 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 th