DNA methylation profiles delineate epigenetic heterogeneity in seminoma and non-seminoma

M Brait; L Maldonado; S Begum; M Loyo; D Wehle; F F Tavora; L H J Looijenga; J Kowalski; Z Zhang; E Rosenbaum; S Halachmi; G J Netto; M O Hoque

doi:10.1038/bjc.2011.468

DNA methylation profiles delineate epigenetic heterogeneity in seminoma and non-seminoma

M Brait, L Maldonado, S Begum, M Loyo, D Wehle, F F Tavora, L H J Looijenga, J Kowalski, Z Zhang, E Rosenbaum, S Halachmi, G J Netto, M O Hoque

Onderzoeksoutput: Bijdrage aan tijdschrift › Artikel › peer review

50 Citaten (Scopus)

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BACKGROUND: It remains important to understand the biology and identify biomarkers for less studied cancers like testicular cancer. The purpose of this study was to determine the methylation frequency of several cancer-related genes in different histological types of testicular cancer and normal testis tissues (NT).

METHODS: DNA was isolated from 43 seminomas (SEs), 14 non-SEs (NSEs) and 23 NT, and was assayed for promoter methylation status of 15 genes by quantitative methylation-specific PCR. The methylation status was evaluated for an association with cancer, and between SEs and NSEs.

RESULTS: We found differential methylation pattern in SEs and NSEs. MGMT, VGF, ER-β and FKBP4 were predominately methylated in NSEs compared with SEs. APC and hMLH1 are shown to be significantly more methylated in both subtypes in comparison with NT. When combining APC, hMLH1, ER-β and FKBP4, it is possible to identify 86% of the NSEs, whereas only 7% of the SEs.

CONCLUSIONS: Our results indicate that the methylation profile of cancer-associated genes in testicular cancer correlates with histological types and show cancer-specific pattern for certain genes. Further methylation analysis, in a larger cohort is needed to elucidate their role in testicular cancer development and potential for therapy, early detection and disease monitoring.

Originele taal-2	Engels
Pagina's (van-tot)	414-23
Aantal pagina's	10
Tijdschrift	British Journal of Cancer
Volume	106
Nummer van het tijdschrift	2
DOI's	https://doi.org/10.1038/bjc.2011.468
Status	Gepubliceerd - 17 jan. 2012
Extern gepubliceerd	Ja

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10.1038/bjc.2011.468

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@article{de76c5aa427e4e379690606ab71bf938,

title = "DNA methylation profiles delineate epigenetic heterogeneity in seminoma and non-seminoma",

abstract = "BACKGROUND: It remains important to understand the biology and identify biomarkers for less studied cancers like testicular cancer. The purpose of this study was to determine the methylation frequency of several cancer-related genes in different histological types of testicular cancer and normal testis tissues (NT).METHODS: DNA was isolated from 43 seminomas (SEs), 14 non-SEs (NSEs) and 23 NT, and was assayed for promoter methylation status of 15 genes by quantitative methylation-specific PCR. The methylation status was evaluated for an association with cancer, and between SEs and NSEs.RESULTS: We found differential methylation pattern in SEs and NSEs. MGMT, VGF, ER-β and FKBP4 were predominately methylated in NSEs compared with SEs. APC and hMLH1 are shown to be significantly more methylated in both subtypes in comparison with NT. When combining APC, hMLH1, ER-β and FKBP4, it is possible to identify 86% of the NSEs, whereas only 7% of the SEs.CONCLUSIONS: Our results indicate that the methylation profile of cancer-associated genes in testicular cancer correlates with histological types and show cancer-specific pattern for certain genes. Further methylation analysis, in a larger cohort is needed to elucidate their role in testicular cancer development and potential for therapy, early detection and disease monitoring.",

keywords = "Adult, Cohort Studies, DNA Methylation, Epigenesis, Genetic, Genetic Heterogeneity, Humans, Male, Middle Aged, Polymerase Chain Reaction, Promoter Regions, Genetic, Seminoma/genetics, Testicular Neoplasms/genetics",

author = "M Brait and L Maldonado and S Begum and M Loyo and D Wehle and Tavora, {F F} and Looijenga, {L H J} and J Kowalski and Z Zhang and E Rosenbaum and S Halachmi and Netto, {G J} and Hoque, {M O}",

note = "Funding Information: This work was supported by National Cancer Institute Grant 1R03CA128060-01A1 (MO Hoque), Career development award to Dr Hoque from Specialised Program of Research Excellence grant P50 CA098252 (PI: T-C Wu). Dr Hoque and Dr Begum are",

year = "2012",

month = jan,

day = "17",

doi = "10.1038/bjc.2011.468",

language = "English",

volume = "106",

pages = "414--23",

journal = "British Journal of Cancer",

issn = "1532-1827",

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T1 - DNA methylation profiles delineate epigenetic heterogeneity in seminoma and non-seminoma

AU - Brait, M

AU - Maldonado, L

AU - Begum, S

AU - Loyo, M

AU - Wehle, D

AU - Tavora, F F

AU - Looijenga, L H J

AU - Kowalski, J

AU - Zhang, Z

AU - Rosenbaum, E

AU - Halachmi, S

AU - Netto, G J

AU - Hoque, M O

N1 - Funding Information: This work was supported by National Cancer Institute Grant 1R03CA128060-01A1 (MO Hoque), Career development award to Dr Hoque from Specialised Program of Research Excellence grant P50 CA098252 (PI: T-C Wu). Dr Hoque and Dr Begum are

PY - 2012/1/17

Y1 - 2012/1/17

N2 - BACKGROUND: It remains important to understand the biology and identify biomarkers for less studied cancers like testicular cancer. The purpose of this study was to determine the methylation frequency of several cancer-related genes in different histological types of testicular cancer and normal testis tissues (NT).METHODS: DNA was isolated from 43 seminomas (SEs), 14 non-SEs (NSEs) and 23 NT, and was assayed for promoter methylation status of 15 genes by quantitative methylation-specific PCR. The methylation status was evaluated for an association with cancer, and between SEs and NSEs.RESULTS: We found differential methylation pattern in SEs and NSEs. MGMT, VGF, ER-β and FKBP4 were predominately methylated in NSEs compared with SEs. APC and hMLH1 are shown to be significantly more methylated in both subtypes in comparison with NT. When combining APC, hMLH1, ER-β and FKBP4, it is possible to identify 86% of the NSEs, whereas only 7% of the SEs.CONCLUSIONS: Our results indicate that the methylation profile of cancer-associated genes in testicular cancer correlates with histological types and show cancer-specific pattern for certain genes. Further methylation analysis, in a larger cohort is needed to elucidate their role in testicular cancer development and potential for therapy, early detection and disease monitoring.

AB - BACKGROUND: It remains important to understand the biology and identify biomarkers for less studied cancers like testicular cancer. The purpose of this study was to determine the methylation frequency of several cancer-related genes in different histological types of testicular cancer and normal testis tissues (NT).METHODS: DNA was isolated from 43 seminomas (SEs), 14 non-SEs (NSEs) and 23 NT, and was assayed for promoter methylation status of 15 genes by quantitative methylation-specific PCR. The methylation status was evaluated for an association with cancer, and between SEs and NSEs.RESULTS: We found differential methylation pattern in SEs and NSEs. MGMT, VGF, ER-β and FKBP4 were predominately methylated in NSEs compared with SEs. APC and hMLH1 are shown to be significantly more methylated in both subtypes in comparison with NT. When combining APC, hMLH1, ER-β and FKBP4, it is possible to identify 86% of the NSEs, whereas only 7% of the SEs.CONCLUSIONS: Our results indicate that the methylation profile of cancer-associated genes in testicular cancer correlates with histological types and show cancer-specific pattern for certain genes. Further methylation analysis, in a larger cohort is needed to elucidate their role in testicular cancer development and potential for therapy, early detection and disease monitoring.

KW - Adult

KW - Cohort Studies

KW - DNA Methylation

KW - Epigenesis, Genetic

KW - Genetic Heterogeneity

KW - Humans

KW - Male

KW - Middle Aged

KW - Polymerase Chain Reaction

KW - Promoter Regions, Genetic

KW - Seminoma/genetics

KW - Testicular Neoplasms/genetics

UR - http://www.scopus.com/inward/record.url?scp=84856425020&partnerID=8YFLogxK

U2 - 10.1038/bjc.2011.468

DO - 10.1038/bjc.2011.468

M3 - Article

C2 - 22068818

SN - 1532-1827

VL - 106

SP - 414

EP - 423

JO - British Journal of Cancer

JF - British Journal of Cancer

IS - 2

ER -

DNA methylation profiles delineate epigenetic heterogeneity in seminoma and non-seminoma

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