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Unique ethnic features of DDX41 mutations in patients with idiopathic cytopenia of undetermined significance, myelodysplastic syndrome, or acute myeloid leukemia

DDX41 mutations are associated with hematologic malignancies including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), but the incidence in idiopathic cytopenia of undetermined significance (ICUS) is unknown. We investigated the incidence, genetic characteristics, and clinical featu...

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Autores principales: Choi, Eun-Ji, Cho, Young-Uk, Hur, Eun-Hye, Jang, Seongsoo, Kim, Nayoung, Park, Han-Seung, Lee, Jung-Hee, Lee, Kyoo-Hyung, Kim, Si-Hwan, Hwang, Sang-Hyun, Seo, Eul-Ju, Park, Chan-Jeoung, Lee, Je-Hwan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Fondazione Ferrata Storti 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8804579/
https://www.ncbi.nlm.nih.gov/pubmed/33626862
http://dx.doi.org/10.3324/haematol.2020.270553
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author Choi, Eun-Ji
Cho, Young-Uk
Hur, Eun-Hye
Jang, Seongsoo
Kim, Nayoung
Park, Han-Seung
Lee, Jung-Hee
Lee, Kyoo-Hyung
Kim, Si-Hwan
Hwang, Sang-Hyun
Seo, Eul-Ju
Park, Chan-Jeoung
Lee, Je-Hwan
author_facet Choi, Eun-Ji
Cho, Young-Uk
Hur, Eun-Hye
Jang, Seongsoo
Kim, Nayoung
Park, Han-Seung
Lee, Jung-Hee
Lee, Kyoo-Hyung
Kim, Si-Hwan
Hwang, Sang-Hyun
Seo, Eul-Ju
Park, Chan-Jeoung
Lee, Je-Hwan
author_sort Choi, Eun-Ji
collection PubMed
description DDX41 mutations are associated with hematologic malignancies including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), but the incidence in idiopathic cytopenia of undetermined significance (ICUS) is unknown. We investigated the incidence, genetic characteristics, and clinical features of DDX41 mutations in Korean patients with ICUS, MDS, or AML. We performed targeted deep sequencing of 61 genes including DDX41 in 457 patients with ICUS (n=75), MDS (n=210), or AML (n=172). Germline DDX41 mutations with causality were identified in 28 (6.1%) patients, of whom 27 (96.4%) had somatic mutations in the other position of DDX41. Germline origins of the DDX41 mutations were confirmed in all of the 11 patients in whom germline-based testing was performed. Of the germline DDX41 mutations, p.V152G (n=10) was most common, followed by p.Y259C (n=8), p.A500fs (n=6), and p.E7* (n=3). Compared with non-mutated patients, patients with a DDX41 mutation were more frequently male, older, had a normal karyotype, low leukocyte count, and hypocellular marrow at diagnosis. Three of the four ICUS patients with germline DDX41 mutations progressed to MDS. The incidence of DDX41 mutations in Korean patients was high and there was a distinct mutation pattern, in that p.V152G was a unique germline variant. ICUS harboring germline DDX41 mutations may be regarded as a hereditary myeloid neoplasm. Germline DDX41 mutations are not uncommon and should be explored when treating patients with myeloid malignancies.
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spelling pubmed-88045792022-02-23 Unique ethnic features of DDX41 mutations in patients with idiopathic cytopenia of undetermined significance, myelodysplastic syndrome, or acute myeloid leukemia Choi, Eun-Ji Cho, Young-Uk Hur, Eun-Hye Jang, Seongsoo Kim, Nayoung Park, Han-Seung Lee, Jung-Hee Lee, Kyoo-Hyung Kim, Si-Hwan Hwang, Sang-Hyun Seo, Eul-Ju Park, Chan-Jeoung Lee, Je-Hwan Haematologica Article DDX41 mutations are associated with hematologic malignancies including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), but the incidence in idiopathic cytopenia of undetermined significance (ICUS) is unknown. We investigated the incidence, genetic characteristics, and clinical features of DDX41 mutations in Korean patients with ICUS, MDS, or AML. We performed targeted deep sequencing of 61 genes including DDX41 in 457 patients with ICUS (n=75), MDS (n=210), or AML (n=172). Germline DDX41 mutations with causality were identified in 28 (6.1%) patients, of whom 27 (96.4%) had somatic mutations in the other position of DDX41. Germline origins of the DDX41 mutations were confirmed in all of the 11 patients in whom germline-based testing was performed. Of the germline DDX41 mutations, p.V152G (n=10) was most common, followed by p.Y259C (n=8), p.A500fs (n=6), and p.E7* (n=3). Compared with non-mutated patients, patients with a DDX41 mutation were more frequently male, older, had a normal karyotype, low leukocyte count, and hypocellular marrow at diagnosis. Three of the four ICUS patients with germline DDX41 mutations progressed to MDS. The incidence of DDX41 mutations in Korean patients was high and there was a distinct mutation pattern, in that p.V152G was a unique germline variant. ICUS harboring germline DDX41 mutations may be regarded as a hereditary myeloid neoplasm. Germline DDX41 mutations are not uncommon and should be explored when treating patients with myeloid malignancies. Fondazione Ferrata Storti 2021-02-25 /pmc/articles/PMC8804579/ /pubmed/33626862 http://dx.doi.org/10.3324/haematol.2020.270553 Text en Copyright© 2022 Ferrata Storti Foundation https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution Noncommercial License (by-nc 4.0) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Article
Choi, Eun-Ji
Cho, Young-Uk
Hur, Eun-Hye
Jang, Seongsoo
Kim, Nayoung
Park, Han-Seung
Lee, Jung-Hee
Lee, Kyoo-Hyung
Kim, Si-Hwan
Hwang, Sang-Hyun
Seo, Eul-Ju
Park, Chan-Jeoung
Lee, Je-Hwan
Unique ethnic features of DDX41 mutations in patients with idiopathic cytopenia of undetermined significance, myelodysplastic syndrome, or acute myeloid leukemia
title Unique ethnic features of DDX41 mutations in patients with idiopathic cytopenia of undetermined significance, myelodysplastic syndrome, or acute myeloid leukemia
title_full Unique ethnic features of DDX41 mutations in patients with idiopathic cytopenia of undetermined significance, myelodysplastic syndrome, or acute myeloid leukemia
title_fullStr Unique ethnic features of DDX41 mutations in patients with idiopathic cytopenia of undetermined significance, myelodysplastic syndrome, or acute myeloid leukemia
title_full_unstemmed Unique ethnic features of DDX41 mutations in patients with idiopathic cytopenia of undetermined significance, myelodysplastic syndrome, or acute myeloid leukemia
title_short Unique ethnic features of DDX41 mutations in patients with idiopathic cytopenia of undetermined significance, myelodysplastic syndrome, or acute myeloid leukemia
title_sort unique ethnic features of ddx41 mutations in patients with idiopathic cytopenia of undetermined significance, myelodysplastic syndrome, or acute myeloid leukemia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8804579/
https://www.ncbi.nlm.nih.gov/pubmed/33626862
http://dx.doi.org/10.3324/haematol.2020.270553
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