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

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

50 Scopus citations

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.

Original language	English (US)
Pages (from-to)	414-423
Number of pages	10
Journal	British Journal of Cancer
Volume	106
Issue number	2
DOIs	https://doi.org/10.1038/bjc.2011.468
State	Published - Jan 17 2012
Externally published	Yes

Keywords

DNA methylation
biomarker
epigenetics
non-seminoma
seminoma
testicular cancer

ASJC Scopus subject areas

Oncology
Cancer Research

Access to Document

10.1038/bjc.2011.468

Cite this

@article{e6e052589f324ae598db503d0240199b,

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 = "DNA methylation, biomarker, epigenetics, non-seminoma, seminoma, testicular cancer",

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 (US)",

volume = "106",

pages = "414--423",

journal = "British Journal of Cancer",

issn = "0007-0920",

publisher = "Nature Publishing Group",

number = "2",

}

TY - JOUR

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 - DNA methylation

KW - biomarker

KW - epigenetics

KW - non-seminoma

KW - seminoma

KW - testicular cancer

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

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

U2 - 10.1038/bjc.2011.468

DO - 10.1038/bjc.2011.468

M3 - Article

C2 - 22068818

AN - SCOPUS:84856425020

SN - 0007-0920

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this