Detection of a cryptic NUP214/ABL1 gene fusion by mate-pair sequencing (MPseq) in a newly diagnosed case of pediatric T-lymphoblastic leukemia

• Published in: Cold Spring Harbor molecular case studies 2019-04, Vol.5 (2), p.a003533
• Main Authors: Peterson, Jess F, Pitel, Beth A, Smoley, Stephanie A, Smadbeck, James B, Johnson, Sarah H, Vasmatzis, George, Koon, Sarah J, Webley, Matthew R, McGrath, Mary, Bayerl, Michael G, Baughn, Linda B, Rowsey, Ross A, Ketterling, Rhett P, Greipp, Patricia T, Hoppman, Nicole L
• Format: Article
• Language: English
• Subjects: Abnormalities; Acute lymphoblastic leukemia; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; BCR-ABL1 gene; Bone marrow; Child, Preschool; Children; Chromosome aberrations; Clonal deletion; Copy number; Cytogenetics; Enzyme inhibitors; Fluorescence; Fluorescence in situ hybridization; Gene fusion; Gene sequencing; Genetic abnormalities; Genomes; High-Throughput Nucleotide Sequencing; Humans; In Situ Hybridization, Fluorescence; Kinases; Leukemia; Lymphatic leukemia; Lymphocytes T; Male; Next-generation sequencing; Nuclear Pore Complex Proteins - genetics; Oncogene Proteins, Fusion - genetics; Pediatrics; Precision Medicine in Practice; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - diagnosis; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - genetics; Protein-tyrosine kinase; Proto-Oncogene Proteins c-abl - genetics; Sequence Analysis, DNA; Therapy; Treatment Outcome; Tyrosine
• ISSN: 2373-2865; 2373-2873
• DOI: 10.1101/mcs.a003533

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematopoietic neoplasm involving the bone marrow and blood that accounts for ∼15% of childhood and 25% of adult ALL. Whereas multiple, recurrent genetic abnormalities have been described in T-ALL, their clinical significance is unclear or controversial. Importantly, rearrangements, most commonly described in -positive B-ALL and -like B-ALL, have been observed in T-ALL and may respond to tyrosine kinase inhibitor (TKI) therapy. We describe a newly diagnosed case of pediatric T-ALL with a fluorescence in situ hybridization abnormality suggesting a partial deletion by a / dual-color dual-fusion probe but that demonstrated a normal result using an break-apart probe. Mate-pair sequencing (MPseq), a next-generation sequencing (NGS)-based technology utilized to detect copy number and structural abnormalities with high resolution and precision throughout the genome, was performed and revealed a / gene fusion that has been demonstrated to be sensitive to TKI therapy. This case demonstrates the power of MPseq to resolve chromosomal abnormalities unappreciable by traditional cytogenetic methodologies and highlights the clinical value of this novel NGS-based technology.