The origin and nature of BTG1 deletions in leukemia

Waanders, Esme

Dr. Esmé Waanders en Dr. Blanca Scheijen in a joint collaboration between the Departments of Human Genetics and Pediatric Oncology have recently published an article in the top journal PLoS Genetics. They provide interesting new insight about the mechanism ofBTG1 deletions in B-cell precursor lymphoblastic leukemia (BCP-ALL). 

Recent studies have eluded on the existence of a complex clonal cellular architecture in acute lymphoblastic leukemia, where multiple subclones contribute to leukemogenesis. In this study, they show that in pediatric BCP-ALL monoallelic deletions in the tumor suppressorBTG1locus, which are found to occur in 9% of the patients studied, result in truncations of the gene rather than in complete allelic losses. Using both genetic and epigenetic approaches, they demonstrate that these deletions most likely originate from illegitimate RAG recombination. Sensitive backtracking using deletion-spanning PCRs revealed that theseBTG1deletions occur in specific BCP-ALL subtypes, with frequencies higher than previously anticipated, often in one minor subclone or in multiple independent subclones within individual patients. Subclones that carry aBTG1deletion at diagnosis can evolve into the major clone at relapse. These findings link a mechanism of tumor suppressor gene deletion to the multiclonal evolution of ALL.

 Esmé Waanders, Blanca Scheijen, Laurens T. van der Meer, Simon V. van Reijmersdal, Liesbeth van Emst, Yvet Kroeze, Edwin Sonneveld, Peter M. Hoogerbrugge, Ad Geurts van Kessel, Frank N. van Leeuwen, and Roland P. Kuiper. The Origin and Nature of Tightly Clustered BTG1 Deletions in Precursor B-cell Acute Lymphoblastic Leukemia Support a Model of Multiclonal Evolution. PLoS Genetics 2012 Febr 16; 8(2): e1002533.

Waanders en Scheijen

Esmé Waanders (left) and Bianca Scheijen (right)

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