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Panel-based next-generation sequencing identifies prognostic and actionable genes in childhood acute lymphoblastic leukemia and is suitable for clinical sequencing

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Abstract

Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Although the cure rate of ALL has greatly improved, a considerable number of patients suffer from relapse of leukemia. Therefore, ALL remains the leading cause of death from cancer during childhood. To improve the cure rate of these patients, precisely detecting patients with high risk of relapse and incorporating new targeted therapies are urgently needed. This study investigated inexpensive, rapid, next-generation sequencing of more than 150 cancer-related genes for matched diagnostic, remission, and relapse samples of 17 patients (3 months to 15 years old) with relapsed ALL. In this analysis, we identified 16 single-nucleotide variants (SNVs) and insertion/deletion variants and 19 copy number variants (CNVs) at diagnosis and 28 SNVs and insertion/deletion variants and 22 CNVs at relapse. With these genetic alterations, we could detect several B cell precursor ALL patients with high-risk gene alterations who were not stratified into the highest-risk group (5/8, 62.5%). We also detected potentially actionable genetic variants in about half of the patients (8/17, 47.1%). Among them, we found that one patient harbored germline TP53 mutation as a secondary finding. This inexpensive, rapid method can be immediately applied as clinical sequencing and could lead to better management of these patients and potential improvement in the survival rate in childhood ALL.

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Acknowledgements

We thank Ellen Knapp, PhD, from Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript.

Availability of data

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Funding

This work was supported by grants from the Japan Agency for Medical Research and Development (AMED).

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Authors and Affiliations

  1. Department of Pediatrics/Pediatric Hematology and Oncology, Okayama University Hospital, 2-5-1, Shikatacho, Kitaku, Okayama, 700-8558, Japan

    Hisashi Ishida, Kosuke Tamefusa, Kiichiro Kanamitsu, Kaori Fujiwara, Kana Washio, Hirokazu Tsukahara & Akira Shimada

  2. Department of Pediatrics, Hokkaido University Hospital, Hokkaido, Japan

    Akihiro Iguchi

  3. Division of Medical Support, Okayama University Hospital, Okayama, Japan

    Michinori Aoe & Takahide Takahashi

  4. Department of BioBank, BioRepository/BioMarker Analysis Center, Okayama University Hospital, Okayama, Japan

    Takehiro Matsubara

  5. Clinical Research Center, National Hospital Organization, Nagoya Medical Center, Nagoya, Aichi, Japan

    Masashi Sanada

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  1. Hisashi Ishida
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  2. Akihiro Iguchi
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Contributions

H.I, A.I, and A.S wrote the manuscript. H.I, M.A, T.T, T.M, M.S., and A.S performed the genetic analysis and interpreted the result. H.I, K.T, K.K, K.F, K.W, H.T, and A.S did the patient’s care and collected the clinical data. All authors reviewed the manuscript.

Corresponding author

Correspondence to Akira Shimada.

Ethics declarations

This study was approved by the institutional ethics committee in Okayama University Hospital and informed consent was obtained for each patient from the legal guardian of the patients and/or themselves. All methods were performed in accordance with the relevant guidelines and regulations.

Conflict of interests

The authors declare that they have no conflict of interest.

Ethical approval

The institutional Review Board of Okayama University Hospital approved this study.

Informed consent

Informed consent was obtained for each patient from the legal guardian of the patients and/or themselves.

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Ishida, H., Iguchi, A., Aoe, M. et al. Panel-based next-generation sequencing identifies prognostic and actionable genes in childhood acute lymphoblastic leukemia and is suitable for clinical sequencing. Ann Hematol 98, 657–668 (2019). https://doi.org/10.1007/s00277-018-3554-8

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  • DOI: https://doi.org/10.1007/s00277-018-3554-8

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