Detailed gene dose analysis reveals recurrent focal gene deletions in pediatric B-cell precursor acute lymphoblastic leukemia

Abstract

To identify copy number alterations (CNAs) in pediatric B-cell precursor acute lymphoblastic leukemia (BCP ALL), array comparative genomic hybridization was performed on 50 cases; detected CNAs were validated in a cohort of 191 cases analyzed by single nucleotide polymorphism arrays. Apart from CNAs involving leukemia-associated genes, recurrent deletions targeting genes not previously implicated in BCP ALL, e.g. INIP, IRF1 and PDE4B, were identified. Deletions of the DNA repair gene INIP were exclusively found in cases with t(12;21), and deletions of SH2B3 were associated with intrachromosomal amplification of chromosome 21 (p < 0.001). A majority of BTLA deletions (7/11; 64%) affected samples with gain of 21q chromosome material, suggesting that BTLA deletions are associated with both germline and somatic gain of chromosome 21. In cases without known risk-associated cytogenetic markers, CNAs associated with adverse prognosis were identified in 50% (10/20), indicating that a majority of these cases could be assigned to distinct genetic subtypes.

Keywords:

• B-Other
• CNA
• copy number
• deletion
• pediatric ALL

Acknowledgements

We thank Joseph W. DePierre (Stockholm University) and Janet Holmén for valuable help with text editing, and Agne Lieden for useful advice regarding interpretation of the data.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article at http://dx.doi.org/10.3109/10428194.2015.1136740.

This study was supported by grants from the Swedish Childhood Cancer Foundation, Karolinska Institutet, and Stockholm County Council.