Investigation of MGMT and DAPK1 methylation patterns in diffuse large B-cell lymphoma using allelic MSP-pyrosequencing

Lasse Sommer Kristensen; Marianne Bach Treppendahl; Fazila Asmar; Mia Seremet Girkov; Helene Myrtue Nielsen; Tina Ellegaard Kjeldsen; Elisabeth Ralfkiaer; Lise Lotte Hansen; Kirsten Grønbæk

doi:10.1038/srep02789

Investigation of MGMT and DAPK1 methylation patterns in diffuse large B-cell lymphoma using allelic MSP-pyrosequencing

Lasse Sommer Kristensen, Marianne Bach Treppendahl, Fazila Asmar, Mia Seremet Girkov, Helene Myrtue Nielsen, Tina Ellegaard Kjeldsen, Elisabeth Ralfkiaer, Lise Lotte Hansen, Kirsten Grønbæk

Department of Clinical Medicine

26 Citations (Scopus)

Abstract

The tumor suppressor genes MGMT and DAPK1 become methylated in several cancers including diffuse large B-cell lymphoma (DLBCL). However, allelic methylation patterns have not been investigated in DLBCL. We developed a fast and cost-efficient method for the analysis of allelic methylation based on pyrosequencing of methylation specific PCR (MSP) products including a SNP. Allelic methylation patterns were reliably analyzed in standards of known allelic methylation status even when diluted in unmethylated DNA to below 1% methylation. When studying 148 DLBCL patients MGMT and DAPK1 methylation was observed in 19% and 89%, respectively, and among methylated and heterozygous patients 29% and 55%, respectively, were biallelically methylated. An association between the T-allele of the rs16906252 SNP and MGMT methylation was observed (p-value = 0.04), and DAPK1 methylation of the A-allele was associated with shorter overall survival (p-value = 0.006). In future cancer research allelic MSP-pyrosequencing may be used to study a wide range of other loci.

Original language	English
Article number	2789
Journal	Scientific Reports
Volume	3
Number of pages	11
ISSN	2045-2322
DOIs	https://doi.org/10.1038/srep02789
Publication status	Published - 2013

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@article{1835798b37b34120b19d885d2321e0ba,

title = "Investigation of MGMT and DAPK1 methylation patterns in diffuse large B-cell lymphoma using allelic MSP-pyrosequencing",

abstract = "The tumor suppressor genes MGMT and DAPK1 become methylated in several cancers including diffuse large B-cell lymphoma (DLBCL). However, allelic methylation patterns have not been investigated in DLBCL. We developed a fast and cost-efficient method for the analysis of allelic methylation based on pyrosequencing of methylation specific PCR (MSP) products including a SNP. Allelic methylation patterns were reliably analyzed in standards of known allelic methylation status even when diluted in unmethylated DNA to below 1% methylation. When studying 148 DLBCL patients MGMT and DAPK1 methylation was observed in 19% and 89%, respectively, and among methylated and heterozygous patients 29% and 55%, respectively, were biallelically methylated. An association between the T-allele of the rs16906252 SNP and MGMT methylation was observed (p-value = 0.04), and DAPK1 methylation of the A-allele was associated with shorter overall survival (p-value = 0.006). In future cancer research allelic MSP-pyrosequencing may be used to study a wide range of other loci.",

author = "Kristensen, {Lasse Sommer} and Treppendahl, {Marianne Bach} and Fazila Asmar and Girkov, {Mia Seremet} and Nielsen, {Helene Myrtue} and Kjeldsen, {Tina Ellegaard} and Elisabeth Ralfkiaer and Hansen, {Lise Lotte} and Kirsten Gr{\o}nb{\ae}k",

year = "2013",

doi = "10.1038/srep02789",

language = "English",

volume = "3",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "nature publishing group",

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TY - JOUR

T1 - Investigation of MGMT and DAPK1 methylation patterns in diffuse large B-cell lymphoma using allelic MSP-pyrosequencing

AU - Kristensen, Lasse Sommer

AU - Treppendahl, Marianne Bach

AU - Asmar, Fazila

AU - Girkov, Mia Seremet

AU - Nielsen, Helene Myrtue

AU - Kjeldsen, Tina Ellegaard

AU - Ralfkiaer, Elisabeth

AU - Hansen, Lise Lotte

AU - Grønbæk, Kirsten

PY - 2013

Y1 - 2013

N2 - The tumor suppressor genes MGMT and DAPK1 become methylated in several cancers including diffuse large B-cell lymphoma (DLBCL). However, allelic methylation patterns have not been investigated in DLBCL. We developed a fast and cost-efficient method for the analysis of allelic methylation based on pyrosequencing of methylation specific PCR (MSP) products including a SNP. Allelic methylation patterns were reliably analyzed in standards of known allelic methylation status even when diluted in unmethylated DNA to below 1% methylation. When studying 148 DLBCL patients MGMT and DAPK1 methylation was observed in 19% and 89%, respectively, and among methylated and heterozygous patients 29% and 55%, respectively, were biallelically methylated. An association between the T-allele of the rs16906252 SNP and MGMT methylation was observed (p-value = 0.04), and DAPK1 methylation of the A-allele was associated with shorter overall survival (p-value = 0.006). In future cancer research allelic MSP-pyrosequencing may be used to study a wide range of other loci.

AB - The tumor suppressor genes MGMT and DAPK1 become methylated in several cancers including diffuse large B-cell lymphoma (DLBCL). However, allelic methylation patterns have not been investigated in DLBCL. We developed a fast and cost-efficient method for the analysis of allelic methylation based on pyrosequencing of methylation specific PCR (MSP) products including a SNP. Allelic methylation patterns were reliably analyzed in standards of known allelic methylation status even when diluted in unmethylated DNA to below 1% methylation. When studying 148 DLBCL patients MGMT and DAPK1 methylation was observed in 19% and 89%, respectively, and among methylated and heterozygous patients 29% and 55%, respectively, were biallelically methylated. An association between the T-allele of the rs16906252 SNP and MGMT methylation was observed (p-value = 0.04), and DAPK1 methylation of the A-allele was associated with shorter overall survival (p-value = 0.006). In future cancer research allelic MSP-pyrosequencing may be used to study a wide range of other loci.

U2 - 10.1038/srep02789

DO - 10.1038/srep02789

M3 - Journal article

C2 - 24071855

SN - 2045-2322

VL - 3

JO - Scientific Reports

JF - Scientific Reports

M1 - 2789

ER -

Investigation of MGMT and DAPK1 methylation patterns in diffuse large B-cell lymphoma using allelic MSP-pyrosequencing

Abstract

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