Recurrent SETBP1 mutations in atypical chronic myeloid leukemia.

Rocco Piazza; Simona Valletta; Nils  Winkelmann; Sara Redaelli; Roberta Spinelli; Alessandra Pirola; Laura Antolini; Luca Mologni; Carla Donadoni; Elli Papaemmanuil; Susanne Schnittger; Dong-Wook Kim; Jacqueline Boultwood; Fabio Rossi; Giuseppe Gaipa; Greta P. De Martini; Paola Francia di Celle; Hyun Gyung Jang; Valeria Fantin; Graham R. Bignell; Vera Magistroni; Torsten Haferlach; Enrico Maria Pogliani; Peter J. Campbell; Andrew J. Chase; William J Tapper; Nicholas C.P. Cross; Carlo Gambacorti-Passerini

doi:10.1038/ng.2495

Recurrent SETBP1 mutations in atypical chronic myeloid leukemia.

Rocco Piazza, Simona Valletta, Nils Winkelmann, Sara Redaelli, Roberta Spinelli, Alessandra Pirola, Laura Antolini, Luca Mologni, Carla Donadoni, Elli Papaemmanuil, Susanne Schnittger, Dong-Wook Kim, Jacqueline Boultwood, Fabio Rossi, Giuseppe Gaipa, Greta P. De Martini, Paola Francia di Celle, Hyun Gyung Jang, Valeria Fantin, Graham R. BignellVera Magistroni, Torsten Haferlach, Enrico Maria Pogliani, Peter J. Campbell, Andrew J. Chase, William J Tapper, Nicholas C.P. Cross, Carlo Gambacorti-Passerini

Division of Cancer Sciences (L5)

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

Abstract

Atypical chronic myeloid leukemia (aCML) shares clinical and laboratory features with CML, but it lacks the BCR-ABL1 fusion. We performed exome sequencing of eight aCMLs and identified somatic alterations of SETBP1 (encoding a p.Gly870Ser alteration) in two cases. Targeted resequencing of 70 aCMLs, 574 diverse hematological malignancies and 344 cancer cell lines identified SETBP1 mutations in 24 cases, including 17 of 70 aCMLs (24.3%; 95% confidence interval (CI) = 16-35%). Most mutations (92%) were located between codons 858 and 871 and were identical to changes seen in individuals with Schinzel-Giedion syndrome. Individuals with mutations had higher white blood cell counts (P = 0.008) and worse prognosis (P = 0.01). The p.Gly870Ser alteration abrogated a site for ubiquitination, and cells exogenously expressing this mutant exhibited higher amounts of SETBP1 and SET protein, lower PP2A activity and higher proliferation rates relative to those expressing the wild-type protein. In summary, mutated SETBP1 represents a newly discovered oncogene present in aCML and closely related diseases.

Original language	English
Pages (from-to)	18-24
Number of pages	7
Journal	Nature Genetics
Volume	45
Issue number	1
DOIs	https://doi.org/10.1038/ng.2495
Publication status	Published - 9 Dec 2012

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/ng.2495

Cite this

Piazza, R., Valletta, S., Winkelmann, N., Redaelli, S., Spinelli, R., Pirola, A., Antolini, L., Mologni, L., Donadoni, C., Papaemmanuil, E., Schnittger, S., Kim, D.-W., Boultwood, J., Rossi, F., Gaipa, G., De Martini, G. P., di Celle, P. F., Jang, H. G., Fantin, V., ... Gambacorti-Passerini, C. (2012). Recurrent SETBP1 mutations in atypical chronic myeloid leukemia. Nature Genetics, 45(1), 18-24. https://doi.org/10.1038/ng.2495

@article{1f8374b1bb5b4d7aaed2d66f077c293e,

title = "Recurrent SETBP1 mutations in atypical chronic myeloid leukemia.",

abstract = "Atypical chronic myeloid leukemia (aCML) shares clinical and laboratory features with CML, but it lacks the BCR-ABL1 fusion. We performed exome sequencing of eight aCMLs and identified somatic alterations of SETBP1 (encoding a p.Gly870Ser alteration) in two cases. Targeted resequencing of 70 aCMLs, 574 diverse hematological malignancies and 344 cancer cell lines identified SETBP1 mutations in 24 cases, including 17 of 70 aCMLs (24.3%; 95% confidence interval (CI) = 16-35%). Most mutations (92%) were located between codons 858 and 871 and were identical to changes seen in individuals with Schinzel-Giedion syndrome. Individuals with mutations had higher white blood cell counts (P = 0.008) and worse prognosis (P = 0.01). The p.Gly870Ser alteration abrogated a site for ubiquitination, and cells exogenously expressing this mutant exhibited higher amounts of SETBP1 and SET protein, lower PP2A activity and higher proliferation rates relative to those expressing the wild-type protein. In summary, mutated SETBP1 represents a newly discovered oncogene present in aCML and closely related diseases.",

author = "Rocco Piazza and Simona Valletta and Nils Winkelmann and Sara Redaelli and Roberta Spinelli and Alessandra Pirola and Laura Antolini and Luca Mologni and Carla Donadoni and Elli Papaemmanuil and Susanne Schnittger and Dong-Wook Kim and Jacqueline Boultwood and Fabio Rossi and Giuseppe Gaipa and {De Martini}, {Greta P.} and {di Celle}, {Paola Francia} and Jang, {Hyun Gyung} and Valeria Fantin and Bignell, {Graham R.} and Vera Magistroni and Torsten Haferlach and Pogliani, {Enrico Maria} and Campbell, {Peter J.} and Chase, {Andrew J.} and Tapper, {William J} and Cross, {Nicholas C.P.} and Carlo Gambacorti-Passerini",

year = "2012",

month = dec,

day = "9",

doi = "10.1038/ng.2495",

language = "English",

volume = "45",

pages = "18--24",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "1",

}

Piazza, R, Valletta, S, Winkelmann, N, Redaelli, S, Spinelli, R, Pirola, A, Antolini, L, Mologni, L, Donadoni, C, Papaemmanuil, E, Schnittger, S, Kim, D-W, Boultwood, J, Rossi, F, Gaipa, G, De Martini, GP, di Celle, PF, Jang, HG, Fantin, V, Bignell, GR, Magistroni, V, Haferlach, T, Pogliani, EM, Campbell, PJ, Chase, AJ, Tapper, WJ, Cross, NCP & Gambacorti-Passerini, C 2012, 'Recurrent SETBP1 mutations in atypical chronic myeloid leukemia.', Nature Genetics, vol. 45, no. 1, pp. 18-24. https://doi.org/10.1038/ng.2495

TY - JOUR

T1 - Recurrent SETBP1 mutations in atypical chronic myeloid leukemia.

AU - Piazza, Rocco

AU - Valletta, Simona

AU - Winkelmann, Nils

AU - Redaelli, Sara

AU - Spinelli, Roberta

AU - Pirola, Alessandra

AU - Antolini, Laura

AU - Mologni, Luca

AU - Donadoni, Carla

AU - Papaemmanuil, Elli

AU - Schnittger, Susanne

AU - Kim, Dong-Wook

AU - Boultwood, Jacqueline

AU - Rossi, Fabio

AU - Gaipa, Giuseppe

AU - De Martini, Greta P.

AU - di Celle, Paola Francia

AU - Jang, Hyun Gyung

AU - Fantin, Valeria

AU - Bignell, Graham R.

AU - Magistroni, Vera

AU - Haferlach, Torsten

AU - Pogliani, Enrico Maria

AU - Campbell, Peter J.

AU - Chase, Andrew J.

AU - Tapper, William J

AU - Cross, Nicholas C.P.

AU - Gambacorti-Passerini, Carlo

PY - 2012/12/9

Y1 - 2012/12/9

N2 - Atypical chronic myeloid leukemia (aCML) shares clinical and laboratory features with CML, but it lacks the BCR-ABL1 fusion. We performed exome sequencing of eight aCMLs and identified somatic alterations of SETBP1 (encoding a p.Gly870Ser alteration) in two cases. Targeted resequencing of 70 aCMLs, 574 diverse hematological malignancies and 344 cancer cell lines identified SETBP1 mutations in 24 cases, including 17 of 70 aCMLs (24.3%; 95% confidence interval (CI) = 16-35%). Most mutations (92%) were located between codons 858 and 871 and were identical to changes seen in individuals with Schinzel-Giedion syndrome. Individuals with mutations had higher white blood cell counts (P = 0.008) and worse prognosis (P = 0.01). The p.Gly870Ser alteration abrogated a site for ubiquitination, and cells exogenously expressing this mutant exhibited higher amounts of SETBP1 and SET protein, lower PP2A activity and higher proliferation rates relative to those expressing the wild-type protein. In summary, mutated SETBP1 represents a newly discovered oncogene present in aCML and closely related diseases.

AB - Atypical chronic myeloid leukemia (aCML) shares clinical and laboratory features with CML, but it lacks the BCR-ABL1 fusion. We performed exome sequencing of eight aCMLs and identified somatic alterations of SETBP1 (encoding a p.Gly870Ser alteration) in two cases. Targeted resequencing of 70 aCMLs, 574 diverse hematological malignancies and 344 cancer cell lines identified SETBP1 mutations in 24 cases, including 17 of 70 aCMLs (24.3%; 95% confidence interval (CI) = 16-35%). Most mutations (92%) were located between codons 858 and 871 and were identical to changes seen in individuals with Schinzel-Giedion syndrome. Individuals with mutations had higher white blood cell counts (P = 0.008) and worse prognosis (P = 0.01). The p.Gly870Ser alteration abrogated a site for ubiquitination, and cells exogenously expressing this mutant exhibited higher amounts of SETBP1 and SET protein, lower PP2A activity and higher proliferation rates relative to those expressing the wild-type protein. In summary, mutated SETBP1 represents a newly discovered oncogene present in aCML and closely related diseases.

UR - https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23222956/?tool=EBI

U2 - 10.1038/ng.2495

DO - 10.1038/ng.2495

M3 - Article

C2 - 23222956

SN - 1061-4036

VL - 45

SP - 18

EP - 24

JO - Nature Genetics

JF - Nature Genetics

IS - 1

ER -

Recurrent SETBP1 mutations in atypical chronic myeloid leukemia.

Abstract

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this