Decoding the DNA Methylome of Mantle Cell Lymphoma in the Light of the Entire B Cell Lineage

A C Queiros; R Beekman; R Vilarrasa-Blasi; M Duran-Ferrer; G Clot; A Merkel; E Raineri; N Russinol; G Castellano; S Bea; A Navarro; M Kulis; N Verdaguer-Dot; P Jares; A Enjuanes; MJ Calasanz; Anke Bergmann; I Vater; I Salaverria; Harmen van de Werken; WH Wilson; A Datta; P Flicek; R Royo; J Martens; E Gine; A Lopez-Guillermo; Hendrik G. Stunnenberg; W Klapper; C Pott; S Heath; I G Gut; R Siebert; E Campo; JI Martin-Subero

doi:10.1016/j.ccell.2016.09.014

Decoding the DNA Methylome of Mantle Cell Lymphoma in the Light of the Entire B Cell Lineage

A C Queiros
, R Beekman
, R Vilarrasa-Blasi
, M Duran-Ferrer
, G Clot
, A Merkel
, E Raineri
, N Russinol
, G Castellano
, S Bea
, A Navarro
, M Kulis
, N Verdaguer-Dot
, P Jares
, A Enjuanes
, MJ Calasanz
, Anke Bergmann
, I Vater
, I Salaverria
, Harmen van de Werken

WH Wilson, A Datta, P Flicek, R Royo, J Martens, E Gine, A Lopez-Guillermo, Hendrik G. Stunnenberg, W Klapper, C Pott, S Heath, I G Gut, R Siebert, E Campo, JI Martin-Subero

Radboud University Medical Center

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

113 Citations (Scopus)

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Abstract

We analyzed the in silico purified DNA methylation signatures of 82 mantle cell lymphomas (MCL) in comparison with cell subpopulations spanning the entire B cell lineage. We identified two MCL subgroups, respectively carrying epigenetic imprints of germinal-center-inexperienced and germinal-center-experienced B cells, and we found that DNA methylation profiles during lymphomagenesis are largely influenced by the methylation dynamics in normal B cells. An integrative epigenomic approach revealed 10,504 differentially methylated regions in regulatory elements marked by H3K27ac in MCL primary cases, including a distant enhancer showing de novo looping to the MCL oncogene SOX11. Finally, we observed that the magnitude of DNA methylation changes per case is highly variable and serves as an independent prognostic factor for MCL outcome.

Original language	English
Pages (from-to)	806-821
Number of pages	16
Journal	Cancer Cell
Volume	30
Issue number	5
DOIs	https://doi.org/10.1016/j.ccell.2016.09.014
Publication status	Published - 14 Nov 2016

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http://hdl.handle.net/1765/95010

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Queiros, A. C., Beekman, R., Vilarrasa-Blasi, R., Duran-Ferrer, M., Clot, G., Merkel, A., Raineri, E., Russinol, N., Castellano, G., Bea, S., Navarro, A., Kulis, M., Verdaguer-Dot, N., Jares, P., Enjuanes, A., Calasanz, MJ., Bergmann, A., Vater, I., Salaverria, I., ... Martin-Subero, JI. (2016). Decoding the DNA Methylome of Mantle Cell Lymphoma in the Light of the Entire B Cell Lineage. Cancer Cell, 30(5), 806-821. https://doi.org/10.1016/j.ccell.2016.09.014

@article{0db5119912394985b546ffa124dfc259,

title = "Decoding the DNA Methylome of Mantle Cell Lymphoma in the Light of the Entire B Cell Lineage",

abstract = "We analyzed the in silico purified DNA methylation signatures of 82 mantle cell lymphomas (MCL) in comparison with cell subpopulations spanning the entire B cell lineage. We identified two MCL subgroups, respectively carrying epigenetic imprints of germinal-center-inexperienced and germinal-center-experienced B cells, and we found that DNA methylation profiles during lymphomagenesis are largely influenced by the methylation dynamics in normal B cells. An integrative epigenomic approach revealed 10,504 differentially methylated regions in regulatory elements marked by H3K27ac in MCL primary cases, including a distant enhancer showing de novo looping to the MCL oncogene SOX11. Finally, we observed that the magnitude of DNA methylation changes per case is highly variable and serves as an independent prognostic factor for MCL outcome.",

author = "Queiros, \{A C\} and R Beekman and R Vilarrasa-Blasi and M Duran-Ferrer and G Clot and A Merkel and E Raineri and N Russinol and G Castellano and S Bea and A Navarro and M Kulis and N Verdaguer-Dot and P Jares and A Enjuanes and MJ Calasanz and Anke Bergmann and I Vater and I Salaverria and \{van de Werken\}, Harmen and WH Wilson and A Datta and P Flicek and R Royo and J Martens and E Gine and A Lopez-Guillermo and Stunnenberg, \{Hendrik G.\} and W Klapper and C Pott and S Heath and Gut, \{I G\} and R Siebert and E Campo and JI Martin-Subero",

year = "2016",

month = nov,

day = "14",

doi = "10.1016/j.ccell.2016.09.014",

language = "English",

volume = "30",

pages = "806--821",

journal = "Cancer Cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "5",

}

Queiros, AC, Beekman, R, Vilarrasa-Blasi, R, Duran-Ferrer, M, Clot, G, Merkel, A, Raineri, E, Russinol, N, Castellano, G, Bea, S, Navarro, A, Kulis, M, Verdaguer-Dot, N, Jares, P, Enjuanes, A, Calasanz, MJ, Bergmann, A, Vater, I, Salaverria, I, van de Werken, H, Wilson, WH, Datta, A, Flicek, P, Royo, R, Martens, J, Gine, E, Lopez-Guillermo, A, Stunnenberg, HG, Klapper, W, Pott, C, Heath, S, Gut, IG, Siebert, R, Campo, E & Martin-Subero, JI 2016, 'Decoding the DNA Methylome of Mantle Cell Lymphoma in the Light of the Entire B Cell Lineage', Cancer Cell, vol. 30, no. 5, pp. 806-821. https://doi.org/10.1016/j.ccell.2016.09.014

TY - JOUR

T1 - Decoding the DNA Methylome of Mantle Cell Lymphoma in the Light of the Entire B Cell Lineage

AU - Queiros, A C

AU - Beekman, R

AU - Vilarrasa-Blasi, R

AU - Duran-Ferrer, M

AU - Clot, G

AU - Merkel, A

AU - Raineri, E

AU - Russinol, N

AU - Castellano, G

AU - Bea, S

AU - Navarro, A

AU - Kulis, M

AU - Verdaguer-Dot, N

AU - Jares, P

AU - Enjuanes, A

AU - Calasanz, MJ

AU - Bergmann, Anke

AU - Vater, I

AU - Salaverria, I

AU - van de Werken, Harmen

AU - Wilson, WH

AU - Datta, A

AU - Flicek, P

AU - Royo, R

AU - Martens, J

AU - Gine, E

AU - Lopez-Guillermo, A

AU - Stunnenberg, Hendrik G.

AU - Klapper, W

AU - Pott, C

AU - Heath, S

AU - Gut, I G

AU - Siebert, R

AU - Campo, E

AU - Martin-Subero, JI

PY - 2016/11/14

Y1 - 2016/11/14

N2 - We analyzed the in silico purified DNA methylation signatures of 82 mantle cell lymphomas (MCL) in comparison with cell subpopulations spanning the entire B cell lineage. We identified two MCL subgroups, respectively carrying epigenetic imprints of germinal-center-inexperienced and germinal-center-experienced B cells, and we found that DNA methylation profiles during lymphomagenesis are largely influenced by the methylation dynamics in normal B cells. An integrative epigenomic approach revealed 10,504 differentially methylated regions in regulatory elements marked by H3K27ac in MCL primary cases, including a distant enhancer showing de novo looping to the MCL oncogene SOX11. Finally, we observed that the magnitude of DNA methylation changes per case is highly variable and serves as an independent prognostic factor for MCL outcome.

AB - We analyzed the in silico purified DNA methylation signatures of 82 mantle cell lymphomas (MCL) in comparison with cell subpopulations spanning the entire B cell lineage. We identified two MCL subgroups, respectively carrying epigenetic imprints of germinal-center-inexperienced and germinal-center-experienced B cells, and we found that DNA methylation profiles during lymphomagenesis are largely influenced by the methylation dynamics in normal B cells. An integrative epigenomic approach revealed 10,504 differentially methylated regions in regulatory elements marked by H3K27ac in MCL primary cases, including a distant enhancer showing de novo looping to the MCL oncogene SOX11. Finally, we observed that the magnitude of DNA methylation changes per case is highly variable and serves as an independent prognostic factor for MCL outcome.

U2 - 10.1016/j.ccell.2016.09.014

DO - 10.1016/j.ccell.2016.09.014

M3 - Article

C2 - 27846393

SN - 1535-6108

VL - 30

SP - 806

EP - 821

JO - Cancer Cell

JF - Cancer Cell

IS - 5

ER -

Decoding the DNA Methylome of Mantle Cell Lymphoma in the Light of the Entire B Cell Lineage

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