Inherited and Somatic Defects in DDX41 in Myeloid Neoplasms

Chantana Polprasert; Isabell Schulze; Mikkael A. Sekeres; Hideki Makishima; Bartlomiej Przychodzen; Naoko Hosono; Jarnail Singh; Richard A. Padgett; Xiaorong Gu; James G. Phillips; Michael Clemente; Yvonne Parker; Daniel Lindner; Brittney Dienes; Eckhard Jankowsky; Yogen Saunthararajah; Yang Du; Kevin Oakley; Nhu Nguyen; Sudipto Mukherjee; Caroline Pabst; Lucy A. Godley; Jane E. Churpek; Daniel A. Pollyea; Utz Krug; Wolfgang E. Berdel; Hans Ulrich Klein; Martin Dugas; Yuichi Shiraishi; Kenichi Chiba; Hiroko Tanaka; Satoru Miyano; Kenichi Yoshida; Seishi Ogawa; Carsten Müller-Tidow; Jaroslaw P. Maciejewski

doi:10.1016/j.ccell.2015.03.017

Inherited and Somatic Defects in DDX41 in Myeloid Neoplasms

Chantana Polprasert, Isabell Schulze, Mikkael A. Sekeres, Hideki Makishima, Bartlomiej Przychodzen, Naoko Hosono, Jarnail Singh, Richard A. Padgett, Xiaorong Gu, James G. Phillips, Michael Clemente, Yvonne Parker, Daniel Lindner, Brittney Dienes, Eckhard Jankowsky, Yogen Saunthararajah, Yang Du, Kevin Oakley, Nhu Nguyen, Sudipto MukherjeeCaroline Pabst, Lucy A. Godley, Jane E. Churpek, Daniel A. Pollyea, Utz Krug, Wolfgang E. Berdel, Hans Ulrich Klein, Martin Dugas, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Kenichi Yoshida, Seishi Ogawa, Carsten Müller-Tidow^*, Jaroslaw P. Maciejewski

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

378 Scopus citations

Abstract

Most cases of adult myeloid neoplasms are routinely assumed to be sporadic. Here, we describe an adult familial acute myeloid leukemia (AML) syndrome caused by germline mutations in the DEAD/H-box helicase gene DDX41. DDX41 was also found to be affected by somatic mutations in sporadic cases of myeloid neoplasms as well as in a biallelic fashion in 50% of patients with germline DDX41 mutations. Moreover, corresponding deletions on 5q35.3 present in 6% of cases led to haploinsufficient DDX41 expression. DDX41 lesions caused altered pre-mRNA splicing and RNA processing. DDX41 is exemplary of other RNA helicase genes also affected by somatic mutations, suggesting that they constitute a family of tumor suppressor genes.

Original language	English
Pages (from-to)	658-670
Number of pages	13
Journal	Cancer Cell
Volume	27
Issue number	5
DOIs	https://doi.org/10.1016/j.ccell.2015.03.017
State	Published - 11 May 2015

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10.1016/j.ccell.2015.03.017

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Polprasert, C., Schulze, I., Sekeres, M. A., Makishima, H., Przychodzen, B., Hosono, N., Singh, J., Padgett, R. A., Gu, X., Phillips, J. G., Clemente, M., Parker, Y., Lindner, D., Dienes, B., Jankowsky, E., Saunthararajah, Y., Du, Y., Oakley, K., Nguyen, N., ... Maciejewski, J. P. (2015). Inherited and Somatic Defects in DDX41 in Myeloid Neoplasms. Cancer Cell, 27(5), 658-670. https://doi.org/10.1016/j.ccell.2015.03.017

@article{a34146aad507444a9cf018b52f28e38d,

title = "Inherited and Somatic Defects in DDX41 in Myeloid Neoplasms",

abstract = "Most cases of adult myeloid neoplasms are routinely assumed to be sporadic. Here, we describe an adult familial acute myeloid leukemia (AML) syndrome caused by germline mutations in the DEAD/H-box helicase gene DDX41. DDX41 was also found to be affected by somatic mutations in sporadic cases of myeloid neoplasms as well as in a biallelic fashion in 50% of patients with germline DDX41 mutations. Moreover, corresponding deletions on 5q35.3 present in 6% of cases led to haploinsufficient DDX41 expression. DDX41 lesions caused altered pre-mRNA splicing and RNA processing. DDX41 is exemplary of other RNA helicase genes also affected by somatic mutations, suggesting that they constitute a family of tumor suppressor genes.",

author = "Chantana Polprasert and Isabell Schulze and Sekeres, {Mikkael A.} and Hideki Makishima and Bartlomiej Przychodzen and Naoko Hosono and Jarnail Singh and Padgett, {Richard A.} and Xiaorong Gu and Phillips, {James G.} and Michael Clemente and Yvonne Parker and Daniel Lindner and Brittney Dienes and Eckhard Jankowsky and Yogen Saunthararajah and Yang Du and Kevin Oakley and Nhu Nguyen and Sudipto Mukherjee and Caroline Pabst and Godley, {Lucy A.} and Churpek, {Jane E.} and Pollyea, {Daniel A.} and Utz Krug and Berdel, {Wolfgang E.} and Klein, {Hans Ulrich} and Martin Dugas and Yuichi Shiraishi and Kenichi Chiba and Hiroko Tanaka and Satoru Miyano and Kenichi Yoshida and Seishi Ogawa and Carsten M{\"u}ller-Tidow and Maciejewski, {Jaroslaw P.}",

note = "Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",

year = "2015",

month = may,

day = "11",

doi = "10.1016/j.ccell.2015.03.017",

language = "English",

volume = "27",

pages = "658--670",

journal = "Cancer Cell",

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Polprasert, C, Schulze, I, Sekeres, MA, Makishima, H, Przychodzen, B, Hosono, N, Singh, J, Padgett, RA, Gu, X, Phillips, JG, Clemente, M, Parker, Y, Lindner, D, Dienes, B, Jankowsky, E, Saunthararajah, Y, Du, Y, Oakley, K, Nguyen, N, Mukherjee, S, Pabst, C, Godley, LA, Churpek, JE, Pollyea, DA, Krug, U, Berdel, WE, Klein, HU, Dugas, M, Shiraishi, Y, Chiba, K, Tanaka, H, Miyano, S, Yoshida, K, Ogawa, S, Müller-Tidow, C & Maciejewski, JP 2015, 'Inherited and Somatic Defects in DDX41 in Myeloid Neoplasms', Cancer Cell, vol. 27, no. 5, pp. 658-670. https://doi.org/10.1016/j.ccell.2015.03.017

TY - JOUR

T1 - Inherited and Somatic Defects in DDX41 in Myeloid Neoplasms

AU - Polprasert, Chantana

AU - Schulze, Isabell

AU - Sekeres, Mikkael A.

AU - Makishima, Hideki

AU - Przychodzen, Bartlomiej

AU - Hosono, Naoko

AU - Singh, Jarnail

AU - Padgett, Richard A.

AU - Gu, Xiaorong

AU - Phillips, James G.

AU - Clemente, Michael

AU - Parker, Yvonne

AU - Lindner, Daniel

AU - Dienes, Brittney

AU - Jankowsky, Eckhard

AU - Saunthararajah, Yogen

AU - Du, Yang

AU - Oakley, Kevin

AU - Nguyen, Nhu

AU - Mukherjee, Sudipto

AU - Pabst, Caroline

AU - Godley, Lucy A.

AU - Churpek, Jane E.

AU - Pollyea, Daniel A.

AU - Krug, Utz

AU - Berdel, Wolfgang E.

AU - Klein, Hans Ulrich

AU - Dugas, Martin

AU - Shiraishi, Yuichi

AU - Chiba, Kenichi

AU - Tanaka, Hiroko

AU - Miyano, Satoru

AU - Yoshida, Kenichi

AU - Ogawa, Seishi

AU - Müller-Tidow, Carsten

AU - Maciejewski, Jaroslaw P.

PY - 2015/5/11

Y1 - 2015/5/11

N2 - Most cases of adult myeloid neoplasms are routinely assumed to be sporadic. Here, we describe an adult familial acute myeloid leukemia (AML) syndrome caused by germline mutations in the DEAD/H-box helicase gene DDX41. DDX41 was also found to be affected by somatic mutations in sporadic cases of myeloid neoplasms as well as in a biallelic fashion in 50% of patients with germline DDX41 mutations. Moreover, corresponding deletions on 5q35.3 present in 6% of cases led to haploinsufficient DDX41 expression. DDX41 lesions caused altered pre-mRNA splicing and RNA processing. DDX41 is exemplary of other RNA helicase genes also affected by somatic mutations, suggesting that they constitute a family of tumor suppressor genes.

AB - Most cases of adult myeloid neoplasms are routinely assumed to be sporadic. Here, we describe an adult familial acute myeloid leukemia (AML) syndrome caused by germline mutations in the DEAD/H-box helicase gene DDX41. DDX41 was also found to be affected by somatic mutations in sporadic cases of myeloid neoplasms as well as in a biallelic fashion in 50% of patients with germline DDX41 mutations. Moreover, corresponding deletions on 5q35.3 present in 6% of cases led to haploinsufficient DDX41 expression. DDX41 lesions caused altered pre-mRNA splicing and RNA processing. DDX41 is exemplary of other RNA helicase genes also affected by somatic mutations, suggesting that they constitute a family of tumor suppressor genes.

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DO - 10.1016/j.ccell.2015.03.017

M3 - Article

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AN - SCOPUS:84929167143

SN - 1535-6108

VL - 27

SP - 658

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JO - Cancer Cell

JF - Cancer Cell

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