Mutational analysis in BCR-ABL1 positive leukemia by deep sequencing based on nanopore MinION technology

• Published in: Experimental and molecular pathology 2017-08, Vol.103 (1), p.33-37
• Main Authors: Minervini, Crescenzio F., Cumbo, Cosimo, Orsini, Paola, Anelli, Luisa, Zagaria, Antonella, Impera, Luciana, Coccaro, Nicoletta, Brunetti, Claudia, Minervini, Angela, Casieri, Paola, Tota, Giuseppina, Russo Rossi, Antonella, Specchia, Giorgina, Albano, Francesco
• Format: Article
• Language: English
• Subjects: ABL1 mutation; Acute lymphoblastic leukemia; Chronic myeloid leukemia; DNA Mutational Analysis; Fusion Proteins, bcr-abl - blood; Fusion Proteins, bcr-abl - genetics; Fusion Proteins, bcr-abl - metabolism; High-Throughput Nucleotide Sequencing; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics; MinION; Mutation; Nanopores; Next generation sequencing; Sensitivity and Specificity
• ISSN: 0014-4800; 1096-0945
• DOI: 10.1016/j.yexmp.2017.06.007

We report a third-generation sequencing assay on nanopore technology (MinION) for detecting BCR-ABL1 KD mutations and compare the results to a Sanger sequencing(SS)-based test in 24 Philadelphia-positive (Ph+) leukemia cases. Our data indicates that MinION is markedly superior to SS in terms of sensitivity, costs and timesaving, and has the added advantage of determining the clonal configuration of multiple mutations. We demonstrate that MinION is suitable for employment in the hematology laboratory for detecting BCR-ABL1 KD mutation in Ph+ leukemias. •We used MinION nanopore sequencing to detect BCR-ABL1 mutations in Ph+ leukemia.•MinION shows greater sensitivity than Sanger sequencing test at competitive costs.•MinION approach allows identifying compound mutations at long distance.