Genomic characterization of pediatric B‐lymphoblastic lymphoma and B‐lymphoblastic leukemia using formalin‐fixed tissues

BackgroundRecurrent genomic changes in B‐lymphoblastic leukemia (B‐ALL) identified by genome‐wide single‐nucleotide polymorphism (SNP) microarray analysis provide important prognostic information, but gene copy number analysis of its rare lymphoma counterpart, B‐lymphoblastic lymphoma (B‐LBL), is limited by the low incidence and lack of fresh tissue for genomic testing.ProcedureWe used molecular inversion probe (MIP) technology to analyze and compare copy number alterations (CNAs) in archival formalin‐fixed paraffin‐embedded pediatric B‐LBL (n = 23) and B‐ALL (n = 55).ResultsSimilar to B‐ALL, CDKN2A/B deletions were the most common alteration identified in 6/23 (26%) B‐LBL cases. Eleven of 23 (48%) B‐LBL patients were hyperdiploid, but none showed triple trisomies (chromosomes 4, 10, and 17) characteristic of B‐ALL. IKZF1 and PAX5 deletions were observed in 13 and 17% of B‐LBL, respectively, which was similar to the reported frequency in B‐ALL. Immunoglobulin light chain lambda (IGL) locus deletions consistent with normal light chain rearrangement were observed in 5/23 (22%) B‐LBL cases, compared with only 1% in B‐ALL samples. None of the B‐LBL cases showed abnormal, isolated VPREB1 deletion adjacent to IGL locus, which we identified in 25% of B‐ALL.ConclusionsOur study demonstrates that the copy number profile of B‐LBL is distinct from B‐ALL, suggesting possible differences in pathogenesis between these closely related diseases.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137353/1/pbc26363.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137353/2/pbc26363_am.pd

Pediatric T- and NK-cell lymphomas: new biologic insights and treatment strategies

T- and natural killer (NK)-cell lymphomas are challenging childhood neoplasms. These cancers have varying presentations, vast molecular heterogeneity, and several are quite unusual in the West, creating diagnostic challenges. Over 20 distinct T- and NK-cell neoplasms are recognized by the 2008 World Health Organization classification, demonstrating the diversity and potential complexity of these cases. In pediatric populations, selection of optimal therapy poses an additional quandary, as most of these malignancies have not been studied in large randomized clinical trials. Despite their rarity, exciting molecular discoveries are yielding insights into these clinicopathologic entities, improving the accuracy of our diagnoses of these cancers, and expanding our ability to effectively treat them, including the use of new targeted therapies. Here, we summarize this fascinating group of lymphomas, with particular attention to the three most common subtypes: T-lymphoblastic lymphoma, anaplastic large cell lymphoma, and peripheral T-cell lymphoma-not otherwise specified. We highlight recent findings regarding their molecular etiologies, new biologic markers, and cutting-edge therapeutic strategies applied to this intriguing class of neoplasms