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.

Carlos A Tirado,Peter Traum,Michael Kallen,Nagesh Rao,Yeun Kim,David Shabsovich,Sheeja Pullarkat

doi:10.1186/s40364-015-0036-1

Carlos A Tirado, Peter Traum + Show 5 more

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https://doi.org/10.1186/s40364-015-0036-1

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Journal: Biomarker Research	Publication Date: Jun 5, 2015
Citations: 21	License type: CC BY 4.0

Affiliation: University of California, Los Angeles

Abstract

BackgroundRearrangements 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.FindingsHerein, 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.ConclusionsTo 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.

Highlights

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
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 Fluorescence in situ hybridization (FISH)
Fluorescence in situ hybridization (FISH) FISH was performed on interphase nuclei and/or previously G-banded metaphase spreads using the following probes acquired from Abbott Molecular (Abbott Molecular, Des Plaines, Illinois 60018): Fig. 1 Abnormal karyotype from metaphase spread seen on G-banded chromosomes in the patient’s bone marrow: 47,XY,+21c[25]/47,idem, t(2;12)(p12;p13),t(8;14)(q11.2;q32)[4]

Summary

Introduction

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. 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. Pediatric B-acute lymphoblastic leukemia (B-ALL) often bears a range of numerical and structural cytogenetic abnormalities, including but not limited to the following, in decreasing frequency: t(12;21)(p13;q22) [ETV6/RUNX1], hyperdiploidy, t(1;19)(q23;p13.3) [PBX1/TCF3], t(4;11)(q21; q23) [AFF1/MLL], hypodiploidy, and t(9;22)(q34;q11.2) [BCR/ABL1] [1]. Abnormalities involving ETV6 are a relatively common finding in B-ALL, the precise leukemogenic role of the gene in the context of some of the aforementioned aberrations remains understudied

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