Incorporation of somatic panels for the detection of haematopoietic transformation in children and young adults with leukaemia predisposition syndromes and with acquired cytopenias
Sharon Noy-Lotan
Pediatric Hematology Laboratory, Felsenstein Medical Research Center, Petach Tikva, Israel
Search for more papers by this authorTanya Krasnov
Pediatric Hematology Laboratory, Felsenstein Medical Research Center, Petach Tikva, Israel
Search for more papers by this authorOrly Dgany
Pediatric Hematology Laboratory, Felsenstein Medical Research Center, Petach Tikva, Israel
Search for more papers by this authorMarta Jeison
Department of Hematology-Oncology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel
Search for more papers by this authorAsaf D. Yanir
Department of Hematology-Oncology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel
Search for more papers by this authorOded Gilad
Department of Hematology-Oncology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Search for more papers by this authorHelen Toledano
Department of Hematology-Oncology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Search for more papers by this authorShlomit Barzilai-Birenboim
Department of Hematology-Oncology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Search for more papers by this authorJoanne Yacobovich
Department of Hematology-Oncology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Search for more papers by this authorShai Izraeli
Department of Hematology-Oncology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Search for more papers by this authorHannah Tamary
Pediatric Hematology Laboratory, Felsenstein Medical Research Center, Petach Tikva, Israel
Department of Hematology-Oncology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Search for more papers by this authorCorresponding Author
Orna Steinberg-Shemer
Pediatric Hematology Laboratory, Felsenstein Medical Research Center, Petach Tikva, Israel
Department of Hematology-Oncology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Correspondence: Orna Steinberg-Shemer, Schneider Children’s Medical Center of Israel, 14 Kaplan Street, PO Box 559, Petach Tikvah 4920235, Israel.
E-mail: [email protected]
Search for more papers by this authorSharon Noy-Lotan
Pediatric Hematology Laboratory, Felsenstein Medical Research Center, Petach Tikva, Israel
Search for more papers by this authorTanya Krasnov
Pediatric Hematology Laboratory, Felsenstein Medical Research Center, Petach Tikva, Israel
Search for more papers by this authorOrly Dgany
Pediatric Hematology Laboratory, Felsenstein Medical Research Center, Petach Tikva, Israel
Search for more papers by this authorMarta Jeison
Department of Hematology-Oncology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel
Search for more papers by this authorAsaf D. Yanir
Department of Hematology-Oncology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel
Search for more papers by this authorOded Gilad
Department of Hematology-Oncology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Search for more papers by this authorHelen Toledano
Department of Hematology-Oncology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Search for more papers by this authorShlomit Barzilai-Birenboim
Department of Hematology-Oncology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Search for more papers by this authorJoanne Yacobovich
Department of Hematology-Oncology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Search for more papers by this authorShai Izraeli
Department of Hematology-Oncology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Search for more papers by this authorHannah Tamary
Pediatric Hematology Laboratory, Felsenstein Medical Research Center, Petach Tikva, Israel
Department of Hematology-Oncology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Search for more papers by this authorCorresponding Author
Orna Steinberg-Shemer
Pediatric Hematology Laboratory, Felsenstein Medical Research Center, Petach Tikva, Israel
Department of Hematology-Oncology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Correspondence: Orna Steinberg-Shemer, Schneider Children’s Medical Center of Israel, 14 Kaplan Street, PO Box 559, Petach Tikvah 4920235, Israel.
E-mail: [email protected]
Search for more papers by this authorSummary
Detection of somatic mutations may help verify the diagnosis of myelodysplastic syndrome (MDS) in patients with persistent cytopenias or with MDS-predisposition syndromes, prior to the development of overt leukemia. However, the spectrum and consequences of acquired changes in paediatric patients have not been fully evaluated, and especially not in the context of an underlying syndrome. We incorporated a targeted next-generation-sequencing panel of 54 genes for the detection of somatic mutations in paediatric and young adult patients with inherited or acquired cytopenias. Sixty-five patients were included in this study, of whom 17 (26%) had somatic mutations. We detected somatic mutations in 20% of individuals with inherited MDS-predisposition syndromes, including in patients with severe congenital neutropenia and Fanconi anaemia, and with germline mutations in SAMD9L. Thirty-eight per cent of children with acquired cytopenias and suspected MDS had somatic changes, most commonly in genes related to signal transduction and transcription. Molecularly abnormal clones often preceded cytogenetic changes. Thus, routine performance of somatic panels can establish the diagnosis of MDS and determine the optimal timing of haematopoietic stem cell transplantation, prior to the development of leukaemia. In addition, performing somatic panels in patients with inherited MDS-predisposition syndromes may reveal their unique spectrum of acquired mutations.
Supporting Information
| Filename | Description |
|---|---|
| bjh17285-sup-0001-TableS1-S3.docxWord document, 33.1 KB |
Table S1. Patient characteristics. Table S2. Somatically mutated genes, cytogenetics and FISH studies in patients with inherited syndromes predisposing to myelodysplastic syndrome/acute myeloid leukemia. Table S3. Somatically mutated genes and cytogenetics and FISH studies in patients with prolonged cytopenias/suspected myelodysplastic syndrome. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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