Premium
Identification of a novel fusion gene involving RUNX1 and the antisense strand of SV2B in a BCR‐ABL1 ‐positive acute leukemia
Author(s) -
Giguère Amélie,
Hébert Josée
Publication year - 2013
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.22105
Subject(s) - runx1 , chromosomal translocation , fusion gene , biology , leukemia , breakpoint cluster region , fusion transcript , abl , microbiology and biotechnology , fusion protein , myeloid leukemia , cancer research , haploinsufficiency , gene , genetics , phenotype , transcription factor , receptor , recombinant dna , tyrosine kinase
RUNX1 , a key regulator of hematopoiesis, is frequently mutated or implicated in chromosomal translocations in acute leukemia. About half of RUNX1 translocations remain uncharacterized at the molecular level. We describe here one such event, a t(15;21)(q26.1;q22) translocation identified in an adult patient diagnosed with a t(9;22)(q34;q11.2)‐positive acute leukemia. This previously unreported rearrangement yields a fusion of RUNX1 with the antisense strand of the SV2B gene, a new translocation partner of RUNX1 , resulting in the expression of out‐of‐frame mRNA chimeric transcripts and the production of putative truncated RUNX1 isoforms. The t(15;21) translocation also dissociates the P1 promoter of RUNX1 from its open reading frame, reducing RUNX1 expression levels in the patient's leukemic cells. Our data suggest that RUNX1 haploinsufficiency collaborates with the BCR‐ABL1 oncogene in this leukemia. The description of this atypical gene fusion is an important addition to the characterization of the pathogenomic mechanisms leading to RUNX1 structural and functional alterations. Furthermore, our data strongly suggests that inadequate dosage of this gene plays an essential role in leukemogenesis. © 2013 Wiley Periodicals, Inc.