title: A case of B-cell acute lymphoblastic leukemia in a child with Down syndrome bearing a t(2;12)(p12;p13) involving ETV6 and biallelic IGH@ rearrangements.
abstract: BACKGROUND
  Rearrangements involving ETV6 (12p13) are among the most common structural abnormalities in pediatric B-cell acute lymphoblastic leukemia (B-ALL) and involve numerous partner genes. Additionally, the t(8;14)(q11.2;q32), which can result in the placement of CEBPD (8q11.2) near the regulatory regions of IGH@ (14q32) and consequent overexpression of CEPBD, occurs at a higher frequency in individuals with Down syndrome-associated ALL (DS-ALL) compared to both the general and pediatric population. The coexistence of cytogenetically detectable ETV6 abnormalities and t(8;14)(q11.2;q32) is a rare occurrence in B-ALL and has only been reported in a single case in the literature.
  
  
  RESULTS
  Herein, we present a case of B-ALL in a 9-year old male with Down syndrome in which conventional cytogenetic analysis revealed two reciprocal translocations: a t(8;14)(q11.2;q32) and a t(2;12)(p12;p13). Interphase and metaphase fluorescence in situ hybridization (FISH) analysis using break apart probes confirmed the involvement of IGH@ and ETV6 in these translocations, respectively. Additionally, interphase FISH revealed a clonal subpopulation bearing biallelic IGH@ rearrangements not observed by conventional cytogenetic analysis.
  
  
  CONCLUSIONS
  To the best of our knowledge, this is the first reported case of B-ALL bearing an ETV6 translocation with a partner gene on the short arm of chromosome 2 confirmed by FISH. Additionally, it is the second reported case of t(8;14)(q11.2;q32)-ALL bearing a concomitant, cytogenetically detectable abnormality involving ETV6. This case provides insight into a novel translocation involving ETV6 as well as potentially unique and understudied mechanisms of clonal evolution in pediatric B-ALL.
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA USA.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Tirado
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA USA.
authors.forename: David
authors.initials: D
authors.lastname: Shabsovich
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA USA.
authors.forename: Yeun
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Traum
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA USA.
authors.forename: Sheeja
authors.initials: S
authors.lastname: Pullarkat
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Kallen
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA USA.
authors.forename: Nagesh
authors.initials: N
authors.lastname: Rao
keywords: B-ALL; Cytogenetics; ETV6; FISH