Frequency and outcome of pediatric acute lymphoblastic leukemia with <i>ZNF384</i> gene rearrangements including a novel translocation resulting in an <i>ARID1B/ZNF384</i> gene fusion

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p><jats:italic>ZNF384</jats:italic> gene rearrangements with multiple partner genes are recurrent in acute leukemia and are most often associated with a precursor B cell immunophenotype. The overall incidence of this genetic category of leukemia is uncertain.</jats:p></jats:sec><jats:sec><jats:title>Procedure</jats:title><jats:p>Patients with <jats:italic>ZNF384</jats:italic> gene rearrangements from a cohort of 240 precursor B cell acute lymphoblastic leukemia (ALL) pediatric patients over a 3.5‐year time period were characterized with detailed cytogenetic, FISH, genomic, and clinical analyses.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Seven of the 240 patients were identified to have <jats:italic>ZNF384</jats:italic> gene rearrangements including partner genes <jats:italic>TCF3</jats:italic> (four patients), <jats:italic>EWSR1</jats:italic> (one patient), <jats:italic>EP300</jats:italic> (one patient), and the novel gene partner <jats:italic>ARID1B</jats:italic> (one patient). The translocations were confirmed by FISH analysis and with RNA sequencing for the <jats:italic>EP300</jats:italic> and <jats:italic>ARID1B</jats:italic> partner genes. Genomic microarray analysis showed an average of 2.7 copy number alterations in each case with no evidence of imbalance at the translocation breakpoints. Six of the patients with <jats:italic>ZNF384</jats:italic> gene rearrangements had precursor B cell ALL with a CD10– immunophenotype and myeloid‐associated antigens. One of the patients also had myeloperoxidase expression and was diagnosed as mixed phenotype B/myeloid acute leukemia. None of the patients have relapsed with event‐free survival ranging from 6 years 2 months to 9 years 2 months.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>This study suggests that the frequency of <jats:italic>ZNF384</jats:italic> gene rearrangement in pediatric precursor B cell ALL is approximately 3%. The <jats:italic>ARID1B</jats:italic> gene, commonly mutated in multiple types of cancer, was identified as an additional <jats:italic>ZNF384</jats:italic> gene fusion partner.</jats:p></jats:sec>