Frequent inactivation of hSRBC in ovarian cancers by promoter CpG island hypermethylation

Seo Y. Tong, Kyung D. Ki, Jong M. Lee, Min J. Kang, Tae K. Ha, Seong I. Chung, Sung-Gil Chi, Seon Kyung Lee

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Objective. To explore the implication of human SRBC gene [serum deprivation response factor-related gene product that binds to the c-kinase (hSRBC)] abnormality in ovarian tumorigenesis. Design. Retrospective study. Setting. Medical center. Sample. Twenty-two epithelial ovarian cancer and six normal ovary tissues. Measures. Mutation and altered expression of hSRBC gene. Methods. hSRBC expression was characterized by polymerase chain reaction (PCR) analysis. Promoter CG dinucleotide (CpG) site methylation was determined using methylation specific PCR and bisulfite sequencing. Results. Expression of hSRBC transcript was easily detectable in all normal tissues we examined, but 50% (two of four) of cancer cell lines and 41% (nine of 22) of primary carcinomas exhibited undetectable or substantially decreased expression. While genomic deletion or somatic mutations of the gene was not identified, its expression was reactivated in tumor cells by 5-aza-2′-deoxycytidine treatment, suggesting epigenetic inactivation of the gene in tumors. Promoter methylation was detected in all nine tumors with low expression but in only one of 13 (7.7%) tumors with normal expression. Bisulfite DNA sequencing analysis of 23 CpG sites within the promoter region revealed that the CpG sites are highly methylated in low-expressing tumors. In addition, promoter CpG sites methylation status showed a tight association with gene expression level. Conclusion. Our data demonstrate that epigenetic inactivation of hSRBC due to aberrant promoter hypermethylation is a common event and might be implicated in human ovarian tumorigenesis.

Original languageEnglish
Pages (from-to)629-635
Number of pages7
JournalActa Obstetricia et Gynecologica Scandinavica
Volume89
Issue number5
DOIs
Publication statusPublished - 2010 May 1

Fingerprint

CpG Islands
Ovarian Neoplasms
Methylation
Neoplasms
decitabine
Epigenomics
Carcinogenesis
Serum Response Factor
Genes
Gene Expression
Polymerase Chain Reaction
Mutation
Gene Silencing
DNA Sequence Analysis
Genetic Promoter Regions
Ovary
Phosphotransferases
Retrospective Studies
Carcinoma
Cell Line

Keywords

  • Gyne-oncology
  • HSRBC
  • Molecular biology
  • Ovarian cancer
  • Promoter hypermethylation
  • Tumor suppressor gene

ASJC Scopus subject areas

  • Obstetrics and Gynaecology

Cite this

Tong, S. Y., Ki, K. D., Lee, J. M., Kang, M. J., Ha, T. K., Chung, S. I., ... Lee, S. K. (2010). Frequent inactivation of hSRBC in ovarian cancers by promoter CpG island hypermethylation. Acta Obstetricia et Gynecologica Scandinavica, 89(5), 629-635. https://doi.org/10.3109/00016341003678443

Frequent inactivation of hSRBC in ovarian cancers by promoter CpG island hypermethylation. / Tong, Seo Y.; Ki, Kyung D.; Lee, Jong M.; Kang, Min J.; Ha, Tae K.; Chung, Seong I.; Chi, Sung-Gil; Lee, Seon Kyung.

In: Acta Obstetricia et Gynecologica Scandinavica, Vol. 89, No. 5, 01.05.2010, p. 629-635.

Research output: Contribution to journalArticle

Tong, Seo Y. ; Ki, Kyung D. ; Lee, Jong M. ; Kang, Min J. ; Ha, Tae K. ; Chung, Seong I. ; Chi, Sung-Gil ; Lee, Seon Kyung. / Frequent inactivation of hSRBC in ovarian cancers by promoter CpG island hypermethylation. In: Acta Obstetricia et Gynecologica Scandinavica. 2010 ; Vol. 89, No. 5. pp. 629-635.
@article{f3437777946a4f1798b33141292eb44f,
title = "Frequent inactivation of hSRBC in ovarian cancers by promoter CpG island hypermethylation",
abstract = "Objective. To explore the implication of human SRBC gene [serum deprivation response factor-related gene product that binds to the c-kinase (hSRBC)] abnormality in ovarian tumorigenesis. Design. Retrospective study. Setting. Medical center. Sample. Twenty-two epithelial ovarian cancer and six normal ovary tissues. Measures. Mutation and altered expression of hSRBC gene. Methods. hSRBC expression was characterized by polymerase chain reaction (PCR) analysis. Promoter CG dinucleotide (CpG) site methylation was determined using methylation specific PCR and bisulfite sequencing. Results. Expression of hSRBC transcript was easily detectable in all normal tissues we examined, but 50{\%} (two of four) of cancer cell lines and 41{\%} (nine of 22) of primary carcinomas exhibited undetectable or substantially decreased expression. While genomic deletion or somatic mutations of the gene was not identified, its expression was reactivated in tumor cells by 5-aza-2′-deoxycytidine treatment, suggesting epigenetic inactivation of the gene in tumors. Promoter methylation was detected in all nine tumors with low expression but in only one of 13 (7.7{\%}) tumors with normal expression. Bisulfite DNA sequencing analysis of 23 CpG sites within the promoter region revealed that the CpG sites are highly methylated in low-expressing tumors. In addition, promoter CpG sites methylation status showed a tight association with gene expression level. Conclusion. Our data demonstrate that epigenetic inactivation of hSRBC due to aberrant promoter hypermethylation is a common event and might be implicated in human ovarian tumorigenesis.",
keywords = "Gyne-oncology, HSRBC, Molecular biology, Ovarian cancer, Promoter hypermethylation, Tumor suppressor gene",
author = "Tong, {Seo Y.} and Ki, {Kyung D.} and Lee, {Jong M.} and Kang, {Min J.} and Ha, {Tae K.} and Chung, {Seong I.} and Sung-Gil Chi and Lee, {Seon Kyung}",
year = "2010",
month = "5",
day = "1",
doi = "10.3109/00016341003678443",
language = "English",
volume = "89",
pages = "629--635",
journal = "Acta Obstetricia et Gynecologica Scandinavica",
issn = "0001-6349",
publisher = "Wiley-Blackwell",
number = "5",

}

TY - JOUR

T1 - Frequent inactivation of hSRBC in ovarian cancers by promoter CpG island hypermethylation

AU - Tong, Seo Y.

AU - Ki, Kyung D.

AU - Lee, Jong M.

AU - Kang, Min J.

AU - Ha, Tae K.

AU - Chung, Seong I.

AU - Chi, Sung-Gil

AU - Lee, Seon Kyung

PY - 2010/5/1

Y1 - 2010/5/1

N2 - Objective. To explore the implication of human SRBC gene [serum deprivation response factor-related gene product that binds to the c-kinase (hSRBC)] abnormality in ovarian tumorigenesis. Design. Retrospective study. Setting. Medical center. Sample. Twenty-two epithelial ovarian cancer and six normal ovary tissues. Measures. Mutation and altered expression of hSRBC gene. Methods. hSRBC expression was characterized by polymerase chain reaction (PCR) analysis. Promoter CG dinucleotide (CpG) site methylation was determined using methylation specific PCR and bisulfite sequencing. Results. Expression of hSRBC transcript was easily detectable in all normal tissues we examined, but 50% (two of four) of cancer cell lines and 41% (nine of 22) of primary carcinomas exhibited undetectable or substantially decreased expression. While genomic deletion or somatic mutations of the gene was not identified, its expression was reactivated in tumor cells by 5-aza-2′-deoxycytidine treatment, suggesting epigenetic inactivation of the gene in tumors. Promoter methylation was detected in all nine tumors with low expression but in only one of 13 (7.7%) tumors with normal expression. Bisulfite DNA sequencing analysis of 23 CpG sites within the promoter region revealed that the CpG sites are highly methylated in low-expressing tumors. In addition, promoter CpG sites methylation status showed a tight association with gene expression level. Conclusion. Our data demonstrate that epigenetic inactivation of hSRBC due to aberrant promoter hypermethylation is a common event and might be implicated in human ovarian tumorigenesis.

AB - Objective. To explore the implication of human SRBC gene [serum deprivation response factor-related gene product that binds to the c-kinase (hSRBC)] abnormality in ovarian tumorigenesis. Design. Retrospective study. Setting. Medical center. Sample. Twenty-two epithelial ovarian cancer and six normal ovary tissues. Measures. Mutation and altered expression of hSRBC gene. Methods. hSRBC expression was characterized by polymerase chain reaction (PCR) analysis. Promoter CG dinucleotide (CpG) site methylation was determined using methylation specific PCR and bisulfite sequencing. Results. Expression of hSRBC transcript was easily detectable in all normal tissues we examined, but 50% (two of four) of cancer cell lines and 41% (nine of 22) of primary carcinomas exhibited undetectable or substantially decreased expression. While genomic deletion or somatic mutations of the gene was not identified, its expression was reactivated in tumor cells by 5-aza-2′-deoxycytidine treatment, suggesting epigenetic inactivation of the gene in tumors. Promoter methylation was detected in all nine tumors with low expression but in only one of 13 (7.7%) tumors with normal expression. Bisulfite DNA sequencing analysis of 23 CpG sites within the promoter region revealed that the CpG sites are highly methylated in low-expressing tumors. In addition, promoter CpG sites methylation status showed a tight association with gene expression level. Conclusion. Our data demonstrate that epigenetic inactivation of hSRBC due to aberrant promoter hypermethylation is a common event and might be implicated in human ovarian tumorigenesis.

KW - Gyne-oncology

KW - HSRBC

KW - Molecular biology

KW - Ovarian cancer

KW - Promoter hypermethylation

KW - Tumor suppressor gene

UR - http://www.scopus.com/inward/record.url?scp=77951841994&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77951841994&partnerID=8YFLogxK

U2 - 10.3109/00016341003678443

DO - 10.3109/00016341003678443

M3 - Article

VL - 89

SP - 629

EP - 635

JO - Acta Obstetricia et Gynecologica Scandinavica

JF - Acta Obstetricia et Gynecologica Scandinavica

SN - 0001-6349

IS - 5

ER -