The detection of gene rearrangements in pediatric leukemia is an essential component of the work-up, with implications for accurate diagnosis, proper risk stratification, and therapeutic decisions, including the use of targeted therapies. The traditional methods of karyotype and fluorescence in situ hybridization are still valuable, but many new assays are also available, with different strengths and weaknesses. These assays include next-generation sequencing–based assays that have the potential for highly multiplexed and/or unbiased detection of rearrangements.
Gene rearrangements are prevalent in pediatric leukemias.
The detection of gene rearrangements is essential for diagnostic, prognostic, and therapeutic decision making.
Many assays are available to detect gene rearrangements, with different strengths and weaknesses, including karyotype, fluorescence in situ hybridization, reverse transcription polymerase chain reaction, DNA sequencing, and RNA sequencing.
Cancer is understood to be a genetic disease. In pediatric leukemias, as in other cancer types, genetic alterations lead to dysregulation of cellular processes and, ultimately, to malignancy. There are many types of clinically significant genetic alterations. General categories of alterations include sequence mutations, such as single nucleotide changes (single nucleotide variants [SNVs]) and small insertions and deletions (indels), and structural mutations, such as copy number changes (copy number variants [CNVs]) and chromosomal rearrangements. Structural mutations gain significance when they result in oncogenic gene fusions or gene dysregulation. Pediatric tumors in particular, which generally have a low overall mutation rate compared with adult tumors, have a high frequency of tumors where a gene rearrangement is the oncogenic driver. , This article provides an overview of different methods to detect these gene rearrangements.