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Methylome profiling reveals distinct alterations in phenotypic and mutational subgroups of myeloproliferative neoplasms

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Methylome profiling reveals distinct alterations in phenotypic and mutational subgroups of myeloproliferative neoplasms. / Nischal, Sangeeta; Bhattacharyya, Sanchari; Christopeit, Maximilian; Yu, Yiting; Zhou, Li; Bhagat, Tushar D; Sohal, Davendra; Will, Britta; Mo, Yongkai; Suzuki, Masako; Pardanani, Animesh; McDevitt, Michael; Maciejewski, Jaroslaw P; Melnick, Ari M; Greally, John M; Steidl, Ulrich; Moliterno, Alison; Verma, Amit.

in: CANCER RES, Jahrgang 73, Nr. 3, 01.02.2013, S. 1076-85.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Nischal, S, Bhattacharyya, S, Christopeit, M, Yu, Y, Zhou, L, Bhagat, TD, Sohal, D, Will, B, Mo, Y, Suzuki, M, Pardanani, A, McDevitt, M, Maciejewski, JP, Melnick, AM, Greally, JM, Steidl, U, Moliterno, A & Verma, A 2013, 'Methylome profiling reveals distinct alterations in phenotypic and mutational subgroups of myeloproliferative neoplasms', CANCER RES, Jg. 73, Nr. 3, S. 1076-85. https://doi.org/10.1158/0008-5472.CAN-12-0735

APA

Nischal, S., Bhattacharyya, S., Christopeit, M., Yu, Y., Zhou, L., Bhagat, T. D., Sohal, D., Will, B., Mo, Y., Suzuki, M., Pardanani, A., McDevitt, M., Maciejewski, J. P., Melnick, A. M., Greally, J. M., Steidl, U., Moliterno, A., & Verma, A. (2013). Methylome profiling reveals distinct alterations in phenotypic and mutational subgroups of myeloproliferative neoplasms. CANCER RES, 73(3), 1076-85. https://doi.org/10.1158/0008-5472.CAN-12-0735

Vancouver

Nischal S, Bhattacharyya S, Christopeit M, Yu Y, Zhou L, Bhagat TD et al. Methylome profiling reveals distinct alterations in phenotypic and mutational subgroups of myeloproliferative neoplasms. CANCER RES. 2013 Feb 1;73(3):1076-85. https://doi.org/10.1158/0008-5472.CAN-12-0735

Bibtex

@article{73f59ec00e3941f0854d0f8c17b595b0,
title = "Methylome profiling reveals distinct alterations in phenotypic and mutational subgroups of myeloproliferative neoplasms",
abstract = "Even though mutations in epigenetic regulators frequently occur in myeloproliferative neoplasms, their effects on the epigenome have not been well studied. Furthermore, even though primary myelofibrosis (PMF) has a markedly worse prognosis than essential thrombocytosis or polycythemia vera, the molecular distinctions between these subgroups are not well elucidated. We conducted the HELP (HpaII tiny fragment enriched by LM-PCR) assay to study genome-wide methylation in polycythemia vera, essential thrombocytosis, and PMF samples compared with healthy controls. We determined that polycythemia vera and essential thrombocytosis are characterized by aberrant promoter hypermethylation, whereas PMF is an epigenetically distinct subgroup characterized by both aberrant hyper- and hypomethylation. Aberrant hypomethylation in PMF was seen to occur in non-CpG island loci, showing further qualitative differences between the disease subgroups. The differentially methylated genes in polycythemia vera and essential thrombocytosis were involved predominantly in cell signaling pathways and were enriched for binding sites of GATA1 and other transcription factors. In contrast, aberrantly methylated genes in PMF were involved in inflammatory pathways and were enriched for NF1, LEF1, and other transcription factors. Within the PMF subgroup, cases with ASXL1 disruptions formed an epigenetically distinct subgroup with relatively increased methylation. Cases of myeloproliferative neoplasms (MPN) with TET2 mutations showed decreased levels of hydroxymethylation and distinct set of hypermethylated genes. In contrast, the JAK2V617F mutation did not drive epigenetic clustering within MPNs. Finally, the significance of aberrant methylation was shown by sensitivity of MPN-derived cell lines to decitabine. These results show epigenetic differences between PMF and polycythemia vera/essential thrombocytosis and reveal methylomic signatures of ASXL1 and TET2 mutations.",
keywords = "Adult, Aged, Aged, 80 and over, Azacitidine, Cell Line, Tumor, DNA Methylation, DNA-Binding Proteins, Female, Humans, Janus Kinase 2, Male, Middle Aged, Mutation, Polycythemia Vera, Primary Myelofibrosis, Proto-Oncogene Proteins, Repressor Proteins, Thrombocythemia, Essential",
author = "Sangeeta Nischal and Sanchari Bhattacharyya and Maximilian Christopeit and Yiting Yu and Li Zhou and Bhagat, {Tushar D} and Davendra Sohal and Britta Will and Yongkai Mo and Masako Suzuki and Animesh Pardanani and Michael McDevitt and Maciejewski, {Jaroslaw P} and Melnick, {Ari M} and Greally, {John M} and Ulrich Steidl and Alison Moliterno and Amit Verma",
year = "2013",
month = feb,
day = "1",
doi = "10.1158/0008-5472.CAN-12-0735",
language = "English",
volume = "73",
pages = "1076--85",
journal = "CANCER RES",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "3",

}

RIS

TY - JOUR

T1 - Methylome profiling reveals distinct alterations in phenotypic and mutational subgroups of myeloproliferative neoplasms

AU - Nischal, Sangeeta

AU - Bhattacharyya, Sanchari

AU - Christopeit, Maximilian

AU - Yu, Yiting

AU - Zhou, Li

AU - Bhagat, Tushar D

AU - Sohal, Davendra

AU - Will, Britta

AU - Mo, Yongkai

AU - Suzuki, Masako

AU - Pardanani, Animesh

AU - McDevitt, Michael

AU - Maciejewski, Jaroslaw P

AU - Melnick, Ari M

AU - Greally, John M

AU - Steidl, Ulrich

AU - Moliterno, Alison

AU - Verma, Amit

PY - 2013/2/1

Y1 - 2013/2/1

N2 - Even though mutations in epigenetic regulators frequently occur in myeloproliferative neoplasms, their effects on the epigenome have not been well studied. Furthermore, even though primary myelofibrosis (PMF) has a markedly worse prognosis than essential thrombocytosis or polycythemia vera, the molecular distinctions between these subgroups are not well elucidated. We conducted the HELP (HpaII tiny fragment enriched by LM-PCR) assay to study genome-wide methylation in polycythemia vera, essential thrombocytosis, and PMF samples compared with healthy controls. We determined that polycythemia vera and essential thrombocytosis are characterized by aberrant promoter hypermethylation, whereas PMF is an epigenetically distinct subgroup characterized by both aberrant hyper- and hypomethylation. Aberrant hypomethylation in PMF was seen to occur in non-CpG island loci, showing further qualitative differences between the disease subgroups. The differentially methylated genes in polycythemia vera and essential thrombocytosis were involved predominantly in cell signaling pathways and were enriched for binding sites of GATA1 and other transcription factors. In contrast, aberrantly methylated genes in PMF were involved in inflammatory pathways and were enriched for NF1, LEF1, and other transcription factors. Within the PMF subgroup, cases with ASXL1 disruptions formed an epigenetically distinct subgroup with relatively increased methylation. Cases of myeloproliferative neoplasms (MPN) with TET2 mutations showed decreased levels of hydroxymethylation and distinct set of hypermethylated genes. In contrast, the JAK2V617F mutation did not drive epigenetic clustering within MPNs. Finally, the significance of aberrant methylation was shown by sensitivity of MPN-derived cell lines to decitabine. These results show epigenetic differences between PMF and polycythemia vera/essential thrombocytosis and reveal methylomic signatures of ASXL1 and TET2 mutations.

AB - Even though mutations in epigenetic regulators frequently occur in myeloproliferative neoplasms, their effects on the epigenome have not been well studied. Furthermore, even though primary myelofibrosis (PMF) has a markedly worse prognosis than essential thrombocytosis or polycythemia vera, the molecular distinctions between these subgroups are not well elucidated. We conducted the HELP (HpaII tiny fragment enriched by LM-PCR) assay to study genome-wide methylation in polycythemia vera, essential thrombocytosis, and PMF samples compared with healthy controls. We determined that polycythemia vera and essential thrombocytosis are characterized by aberrant promoter hypermethylation, whereas PMF is an epigenetically distinct subgroup characterized by both aberrant hyper- and hypomethylation. Aberrant hypomethylation in PMF was seen to occur in non-CpG island loci, showing further qualitative differences between the disease subgroups. The differentially methylated genes in polycythemia vera and essential thrombocytosis were involved predominantly in cell signaling pathways and were enriched for binding sites of GATA1 and other transcription factors. In contrast, aberrantly methylated genes in PMF were involved in inflammatory pathways and were enriched for NF1, LEF1, and other transcription factors. Within the PMF subgroup, cases with ASXL1 disruptions formed an epigenetically distinct subgroup with relatively increased methylation. Cases of myeloproliferative neoplasms (MPN) with TET2 mutations showed decreased levels of hydroxymethylation and distinct set of hypermethylated genes. In contrast, the JAK2V617F mutation did not drive epigenetic clustering within MPNs. Finally, the significance of aberrant methylation was shown by sensitivity of MPN-derived cell lines to decitabine. These results show epigenetic differences between PMF and polycythemia vera/essential thrombocytosis and reveal methylomic signatures of ASXL1 and TET2 mutations.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Azacitidine

KW - Cell Line, Tumor

KW - DNA Methylation

KW - DNA-Binding Proteins

KW - Female

KW - Humans

KW - Janus Kinase 2

KW - Male

KW - Middle Aged

KW - Mutation

KW - Polycythemia Vera

KW - Primary Myelofibrosis

KW - Proto-Oncogene Proteins

KW - Repressor Proteins

KW - Thrombocythemia, Essential

U2 - 10.1158/0008-5472.CAN-12-0735

DO - 10.1158/0008-5472.CAN-12-0735

M3 - SCORING: Journal article

C2 - 23066032

VL - 73

SP - 1076

EP - 1085

JO - CANCER RES

JF - CANCER RES

SN - 0008-5472

IS - 3

ER -