24. Clinical utility of mate pair sequencing as a reflex test in B-lymphoblastic leukemia/lymphoma

      B-lymphoblastic leukemia/lymphoma (B-ALL/LBL) is the most common cancer in children and adolescents and the second-most common leukemia in adults, with nearly 6,000 new diagnoses each year. Karyotype, FISH panels, and in some cases chromosomal microarray studies, are performed for patients with a new diagnosis of B-ALL/LBL. However, approximately 5-10 percent of B-ALL/LBL patients have an unidentified driver mutation or a result of uncertain significance (for example, an atypical FISH signal pattern) despite the combination of chromosome, FISH, and chromosomal microarray testing. Our laboratory has been utilizing mate pair sequencing (MPseq) as a reflex assay for a variety of situations in which karyotype, FISH, and/or microarray fail to adequately characterize genomic abnormalities that may have prognostic and/or therapeutic significance. To date, we have evaluated 46 cases of B-ALL/LBL. MPseq successfully identified the rearrangement in question in 43 of 46 (93.5%) patients. Abnormalities not detected were very low level (<10%) abnormalities or had breakpoints in repetitive genomic regions. Of the 43 successful cases, 13 (30.2%) gained additional prognostic information and 15 (34.9%) gained significant therapeutic information due to the MPseq results. Overall, 58.1% of the patients received additional therapeutic and/or prognostic information from the MPseq result. These results demonstrate the significant clinical utility of using MPseq as a supplement to traditional cytogenetic techniques in B-ALL/LBL. Taken together with previous studies performed by our laboratory, these data suggest MPseq could replace traditional cytogenetic testing in new leukemia diagnoses. Case examples, as well as potential modifications (both short-term and long-term) of B-ALL/LBL testing algorithms will be presented. Implementation of testing algorithms incorporating MPseq will likely result in increased detection rate for driver mutations and more accurate prognostic stratification for patients with B-ALL/LBL.
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