Characterization of <i>PAX5</i> intragenic tandem multiplication in pediatric B-lymphoblastic leukemia by optical genome mapping
Jeffrey Jean, Alexandra E. Kovach, Andrew Doan, Matthew J. Oberley, Jianling Ji, Ryan J. Schmidt, Jaclyn A. Biegel, Deepa Bhojwani, Gordana Raca
Abstract
The PAX5 (paired-box domain gene 5) gene encodes a transcription factor with a key role in regulating B-cell differentiation. 1 PAX5 abnormalities are observed in 30% of B-lymphoblastic leukemia (B-ALL) cases, occurring as secondary changes in association with different subtype-defining genetic drivers, 2 but recently also described as primary oncogenic alterations in 2 novel genetic subtypes of the disease: PAX5 P80R and PAX5Alt. rare but recurrent PAX5 abnormality in B-ALL is the presence of multiple additional copies of several exons within the 5 9 end of the gene, referred to as "PAX5 intragenic tandem multiplication (PAX5-ITM)" or "PAX5 intragenic amplification" in the literature. These include the number of extra copies of the affected region, their position and orientation within the gene, and the effects of the extra copies on the structure and function of the PAX5 gene and protein.