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Germline SAMD9 mutation in siblings with monosomy 7 and myelodysplastic syndrome

Leukemia volume 31, pages 1827–1830 (2017)Cite this article

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Myelodysplastic syndromes (MDS) are poorly understood and rare hematologic malignancies in children. In recent years, several germline mutations have been implicated in a subset of familial cases of MDS, other myeloid neoplasms or bone marrow failure syndromes including mutations in GATA2, ETV6 and DDX41.1, 2 However, for some families, such as those first reported nearly 30 years ago,3, 4 who present with MDS and monosomy 7 (OMIM 252270), the predisposing genetic alteration has remained elusive. Here we report our findings on a family without historical suggestions of MDS/AML predisposition but with three siblings with monosomy 7 and MDS.

Bone marrow samples from the three siblings were banked for research after informed consent was obtained. All studies were approved by the Institutional Review Board at St Jude Children’s Research Hospital. Cryopreserved marrow samples were flow-sorted into lymphocyte (source of ‘germline’ DNA), as an alternate source of germline DNA was not available,5 and bulk myeloid populations. Whole exome sequencing was performed on paired tumor/normal samples from the three siblings. Whole genome sequencing was also performed on the paired samples from Sibling 2 and only the normal samples from Siblings 1 and 3. Genomic data have been deposited in the European Genome-Phenome Archive (EGAS00001002202).

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Acknowledgements

We thank the family in this study and for the clinical staff involved in their care and management. We thank Tina Motroni for BM histology images and the Hartwell Center at SJCRH for providing sequencing assistance. This work was funded in part by the American Lebanese and Syrian Associated Charities (ALSAC) of SJCRH and the US National Institutes of Health (K08 HL116605-JMK). JMK holds a Career Award for Medical Scientists from the Burroughs Wellcome Fund.

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Author notes

  1. J R Schwartz and S Wang: These two authors contributed equally to this work.

Authors and Affiliations

  1. Department of Oncology, St. Jude Children’s Research Hospital, Memphis, TN, USA

    J R Schwartz, R B McGee, C Kesserwan, K E Nichols & R C Ribeiro

  2. Department of Computational Biology, St. Jude Children’s Research Hospital, Memphis, TN, USA

    S Wang & G Wu

  3. Department of Pathology, St. Jude Children’s Research Hospital, Memphis, TN, USA

    J Ma, T Lamprecht, M Walsh, G Song, S C Raimondi & J M Klco

  4. Department of Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    M F Walsh

  5. Department of Hematology/Oncology, Joe DiMaggio Children's Hospital, Hollywood, FL, USA

    B E Cauff

  6. Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, University of Freiburg, Freiburg, Germany

    M Wlodarski

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  1. J R Schwartz
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Corresponding authors

Correspondence to M Wlodarski or J M Klco.

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Schwartz, J., Wang, S., Ma, J. et al. Germline SAMD9 mutation in siblings with monosomy 7 and myelodysplastic syndrome. Leukemia 31, 1827–1830 (2017). https://doi.org/10.1038/leu.2017.142

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