Methylation profiles of hereditary and sporadic ovarian cancer

Guus M. Bol, Karijn P M Suijkerbuijk, Joost Bart, Marc Vooijs, Elsken Van Der Wall, Paul J. Van Diest

Research output: Contribution to journalArticle

Abstract

Aims: Tumour suppressor gene silencing through promoter hypermethylation plays an important role in oncogenesis. Carcinogenesis of hereditary cancers usually differs from that of their sporadic counterparts, but methylation has hardly been studied in hereditary ovarian cancer. The aim of this study was to investigate promoter methylation of a set of common tumour suppressor genes in BRCA1-related ovarian cancer in comparison with sporadic ovarian cancer. Methods and results: Methylation-specific multiplex ligation-dependent probe amplification was used to assess the extent of promoter methylation of 24 different tumour suppressor genes in BRCA1-associated (n = 25) and matched sporadic ovarian tumours (n = 50). A cumulative methylation index (CMI) was calculated and differences between individual genes were analysed. There was no significant difference in cumulative methylation between BRCA1-associated and sporadic ovarian carcinomas (median CMI 108; CMI 110; P = 0.86). Also, methylation patterns of individual genes did not show distinct differences after correction for multiple comparisons. CDH13, GSTP1 and RASSF1 were frequently methylated in both sporadic and hereditary ovarian cancers. BRCA1 methylation occurred in 14% of sporadic tumours, but was not detected in BRCA1-associated tumours. Conclusions: CDH13, GSTP1 and RASSF1 are frequently methylated in both sporadic and BRCA1-associated ovarian cancers. Interestingly, methylation of BRCA1, while frequent in sporadic ovarian cancer, never occurred in the hereditary group. BRCA1-associated ovarian cancers mimic their sporadic counterparts in extent and pattern of promoter methylation of several common tumour suppressor genes. This finding could have implications for future chemotherapy regimens based on epigenetic changes.

Original languageEnglish (US)
Pages (from-to)363-370
Number of pages8
JournalHistopathology
Volume57
Issue number3
DOIs
StatePublished - Sep 2010
Externally publishedYes

Fingerprint

Ovarian Neoplasms
Methylation
Tumor Suppressor Genes
Neoplasms
Carcinogenesis
Multiplex Polymerase Chain Reaction
Gene Silencing
Epigenomics
Individuality
Genes
Carcinoma
Drug Therapy

Keywords

  • BRCA1 gene
  • hereditary
  • methylation
  • MS-MLPA
  • neoplastic syndromes
  • ovarian neoplasms

ASJC Scopus subject areas

  • Histology
  • Pathology and Forensic Medicine

Cite this

Bol, G. M., Suijkerbuijk, K. P. M., Bart, J., Vooijs, M., Van Der Wall, E., & Van Diest, P. J. (2010). Methylation profiles of hereditary and sporadic ovarian cancer. Histopathology, 57(3), 363-370. https://doi.org/10.1111/j.1365-2559.2010.03642.x

Methylation profiles of hereditary and sporadic ovarian cancer. / Bol, Guus M.; Suijkerbuijk, Karijn P M; Bart, Joost; Vooijs, Marc; Van Der Wall, Elsken; Van Diest, Paul J.

In: Histopathology, Vol. 57, No. 3, 09.2010, p. 363-370.

Research output: Contribution to journalArticle

Bol, GM, Suijkerbuijk, KPM, Bart, J, Vooijs, M, Van Der Wall, E & Van Diest, PJ 2010, 'Methylation profiles of hereditary and sporadic ovarian cancer', Histopathology, vol. 57, no. 3, pp. 363-370. https://doi.org/10.1111/j.1365-2559.2010.03642.x
Bol GM, Suijkerbuijk KPM, Bart J, Vooijs M, Van Der Wall E, Van Diest PJ. Methylation profiles of hereditary and sporadic ovarian cancer. Histopathology. 2010 Sep;57(3):363-370. https://doi.org/10.1111/j.1365-2559.2010.03642.x
Bol, Guus M. ; Suijkerbuijk, Karijn P M ; Bart, Joost ; Vooijs, Marc ; Van Der Wall, Elsken ; Van Diest, Paul J. / Methylation profiles of hereditary and sporadic ovarian cancer. In: Histopathology. 2010 ; Vol. 57, No. 3. pp. 363-370.
@article{621c49334ca54ad5a917816aa141fd78,
title = "Methylation profiles of hereditary and sporadic ovarian cancer",
abstract = "Aims: Tumour suppressor gene silencing through promoter hypermethylation plays an important role in oncogenesis. Carcinogenesis of hereditary cancers usually differs from that of their sporadic counterparts, but methylation has hardly been studied in hereditary ovarian cancer. The aim of this study was to investigate promoter methylation of a set of common tumour suppressor genes in BRCA1-related ovarian cancer in comparison with sporadic ovarian cancer. Methods and results: Methylation-specific multiplex ligation-dependent probe amplification was used to assess the extent of promoter methylation of 24 different tumour suppressor genes in BRCA1-associated (n = 25) and matched sporadic ovarian tumours (n = 50). A cumulative methylation index (CMI) was calculated and differences between individual genes were analysed. There was no significant difference in cumulative methylation between BRCA1-associated and sporadic ovarian carcinomas (median CMI 108; CMI 110; P = 0.86). Also, methylation patterns of individual genes did not show distinct differences after correction for multiple comparisons. CDH13, GSTP1 and RASSF1 were frequently methylated in both sporadic and hereditary ovarian cancers. BRCA1 methylation occurred in 14{\%} of sporadic tumours, but was not detected in BRCA1-associated tumours. Conclusions: CDH13, GSTP1 and RASSF1 are frequently methylated in both sporadic and BRCA1-associated ovarian cancers. Interestingly, methylation of BRCA1, while frequent in sporadic ovarian cancer, never occurred in the hereditary group. BRCA1-associated ovarian cancers mimic their sporadic counterparts in extent and pattern of promoter methylation of several common tumour suppressor genes. This finding could have implications for future chemotherapy regimens based on epigenetic changes.",
keywords = "BRCA1 gene, hereditary, methylation, MS-MLPA, neoplastic syndromes, ovarian neoplasms",
author = "Bol, {Guus M.} and Suijkerbuijk, {Karijn P M} and Joost Bart and Marc Vooijs and {Van Der Wall}, Elsken and {Van Diest}, {Paul J.}",
year = "2010",
month = "9",
doi = "10.1111/j.1365-2559.2010.03642.x",
language = "English (US)",
volume = "57",
pages = "363--370",
journal = "Histopathology",
issn = "0309-0167",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Methylation profiles of hereditary and sporadic ovarian cancer

AU - Bol, Guus M.

AU - Suijkerbuijk, Karijn P M

AU - Bart, Joost

AU - Vooijs, Marc

AU - Van Der Wall, Elsken

AU - Van Diest, Paul J.

PY - 2010/9

Y1 - 2010/9

N2 - Aims: Tumour suppressor gene silencing through promoter hypermethylation plays an important role in oncogenesis. Carcinogenesis of hereditary cancers usually differs from that of their sporadic counterparts, but methylation has hardly been studied in hereditary ovarian cancer. The aim of this study was to investigate promoter methylation of a set of common tumour suppressor genes in BRCA1-related ovarian cancer in comparison with sporadic ovarian cancer. Methods and results: Methylation-specific multiplex ligation-dependent probe amplification was used to assess the extent of promoter methylation of 24 different tumour suppressor genes in BRCA1-associated (n = 25) and matched sporadic ovarian tumours (n = 50). A cumulative methylation index (CMI) was calculated and differences between individual genes were analysed. There was no significant difference in cumulative methylation between BRCA1-associated and sporadic ovarian carcinomas (median CMI 108; CMI 110; P = 0.86). Also, methylation patterns of individual genes did not show distinct differences after correction for multiple comparisons. CDH13, GSTP1 and RASSF1 were frequently methylated in both sporadic and hereditary ovarian cancers. BRCA1 methylation occurred in 14% of sporadic tumours, but was not detected in BRCA1-associated tumours. Conclusions: CDH13, GSTP1 and RASSF1 are frequently methylated in both sporadic and BRCA1-associated ovarian cancers. Interestingly, methylation of BRCA1, while frequent in sporadic ovarian cancer, never occurred in the hereditary group. BRCA1-associated ovarian cancers mimic their sporadic counterparts in extent and pattern of promoter methylation of several common tumour suppressor genes. This finding could have implications for future chemotherapy regimens based on epigenetic changes.

AB - Aims: Tumour suppressor gene silencing through promoter hypermethylation plays an important role in oncogenesis. Carcinogenesis of hereditary cancers usually differs from that of their sporadic counterparts, but methylation has hardly been studied in hereditary ovarian cancer. The aim of this study was to investigate promoter methylation of a set of common tumour suppressor genes in BRCA1-related ovarian cancer in comparison with sporadic ovarian cancer. Methods and results: Methylation-specific multiplex ligation-dependent probe amplification was used to assess the extent of promoter methylation of 24 different tumour suppressor genes in BRCA1-associated (n = 25) and matched sporadic ovarian tumours (n = 50). A cumulative methylation index (CMI) was calculated and differences between individual genes were analysed. There was no significant difference in cumulative methylation between BRCA1-associated and sporadic ovarian carcinomas (median CMI 108; CMI 110; P = 0.86). Also, methylation patterns of individual genes did not show distinct differences after correction for multiple comparisons. CDH13, GSTP1 and RASSF1 were frequently methylated in both sporadic and hereditary ovarian cancers. BRCA1 methylation occurred in 14% of sporadic tumours, but was not detected in BRCA1-associated tumours. Conclusions: CDH13, GSTP1 and RASSF1 are frequently methylated in both sporadic and BRCA1-associated ovarian cancers. Interestingly, methylation of BRCA1, while frequent in sporadic ovarian cancer, never occurred in the hereditary group. BRCA1-associated ovarian cancers mimic their sporadic counterparts in extent and pattern of promoter methylation of several common tumour suppressor genes. This finding could have implications for future chemotherapy regimens based on epigenetic changes.

KW - BRCA1 gene

KW - hereditary

KW - methylation

KW - MS-MLPA

KW - neoplastic syndromes

KW - ovarian neoplasms

UR - http://www.scopus.com/inward/record.url?scp=77956645106&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77956645106&partnerID=8YFLogxK

U2 - 10.1111/j.1365-2559.2010.03642.x

DO - 10.1111/j.1365-2559.2010.03642.x

M3 - Article

VL - 57

SP - 363

EP - 370

JO - Histopathology

JF - Histopathology

SN - 0309-0167

IS - 3

ER -