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Simultaneous detection of ABL 1 mutation and IKZF 1 deletion in Philadelphia chromosome‐positive acute lymphoblastic leukemia using a customized target enrichment system panel
Author(s) -
Aoe M.,
Ishida H.,
Matsubara T.,
Karakawa S.,
Kawaguchi H.,
Fujiwara K.,
Kanamitsu K.,
Washio K.,
Okada K.,
Shibakura M.,
Shimada A.
Publication year - 2018
Publication title -
international journal of laboratory hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.705
H-Index - 55
eISSN - 1751-553X
pISSN - 1751-5521
DOI - 10.1111/ijlh.12805
Subject(s) - multiplex ligation dependent probe amplification , indel , indel mutation , copy number variation , genetics , sanger sequencing , abl , biology , exon , mutation , gene , multiplex , tyrosine kinase , single nucleotide polymorphism , genotype , receptor , genome
Recent clinical outcomes of pediatric Philadelphia chromosome‐positive acute lymphoblastic leukemia (Ph+ ALL ) vastly improved owing to tyrosine kinase inhibitor ( TKI ). However, the genetic status would be different in each case with ABL 1 gene mutation or copy number variants ( CNV s) such as IKZF 1 deletion. In particular, the TKI resistant clone with ABL 1 kinase mutation remains problematic. The comprehensive assessment of genetic status including mutation, insertion and deletion (indel) and CNV s is necessary. Methods We evaluated a next‐generation sequencing ( NGS )‐based customized HaloPlex target enrichment system panel to simultaneously detect coding mutations, indel and CNV s. We analysed approximately 160 known genes associated with hematological disorders in 5 pediatric Ph+ ALL patients. Results Mono‐allelic IKZF 1 deletions were found in 4 patients at diagnosis. Furthermore, the mono‐allelic deletions were found in exons of RB 1 , EBF 1 , PAX 5 and ETV 6 genes. Bi‐allelic deletions were detected in CDKN 2A and CDKN 2B genes in 1 patient. ABL 1 mutation was also detected in 1 patient at relapse. These results were almost comparable with the results of the multiplex ligation‐dependent probe amplification ( MLPA ) method or Sanger sequence. Conclusion Next‐generation sequencing‐based custom HaloPlex target enrichment system panel allows us to detect the coding mutations, indel, and CNV s in pediatric Ph+ ALL simultaneously, and its results seem comparable with those of other methods.