Genetic and epigenetic inactivation of TNFRSFI0C in human prostate cancer

Yu Cheng, Jin Woo Kim, Wennuan Liu, Thomas A. Dunn, Jun Luo, Matthew J. Loza, Seong Tae Kim, Siqun Lilly Zheng, Jianfeng Xu, William B Isaacs, Bao Li Chang

Research output: Contribution to journalArticle

Abstract

BACKGROUND. TNFRSF10C, is located on 8p21.3, one of the most frequently deleted loci in the genome of prostate cancer (PCa). Hypermethylation of TNFRSF10C promoter CpG island (CGI) had been reported in many tumors including PCa. However, the interplay between somatic deletion and promoter hypermethylation of TNFRSF10C on PCa development has not been investigated. METHODS. Methylation status of promoter CGI and deletion status of the TNFRSF10C locus was investigated by bisulfite sequencing and Affymetrix SNP array, respectively, in 59 pairs of PCa tumor and matched normal samples with three PCa cell lines. TNFRSF10C gene expression changes in relation to cancer-associated genetic/epigenetic changes in clinical specimens, and change of TNFRSF10C expression before and after 5-aza-20-deoxycytidine treatment in the PC3 PCa cell line was assessed by real-time RT-PCR. RESULTS. We found that TNFRSF10C promoter CGI was differentially methylated in 46 of 59 primary cancers (78.0%). Hemizygous deletion at TNFRSF10C was found in 44 of the 59 prostate tumors (74.5%). Interestingly, in 94.9% of the tumors (56 out of 59), TNFRSF10C was either hemizygously deleted or its promoter CGI hypermethylated. Deletion and/or methylation of the TNFRSF10C gene were correlated with decreased mRNA expression of the gene in clinical specimens. Demethylation of the TNFRSF10C promoter CGI was accompanied by transcriptional re-activation of TNFRSF10C in the PCa cell line PC3. CONCLUSION. We found a notably high frequency of promoter CGI methylation and deletion of TNFRSF10C in PCa tissues. Our results indicated that inactivation of TNFRSF10C by chromosomal deletion and promoter methylation may play an important role in PCa development.

Original languageEnglish (US)
Pages (from-to)327-335
Number of pages9
JournalProstate
Volume69
Issue number3
DOIs
StatePublished - Feb 15 2009

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Epigenomics
Prostatic Neoplasms
CpG Islands
Methylation
Neoplasms
Cell Line
Gene Expression
Deoxycytidine
Transcriptional Activation
Single Nucleotide Polymorphism
Real-Time Polymerase Chain Reaction
Prostate
Genome
Messenger RNA
Genes

Keywords

  • CpG islands
  • Promoter methylation
  • Somatic copy number alterations

ASJC Scopus subject areas

  • Urology
  • Oncology
  • Medicine(all)

Cite this

Cheng, Y., Kim, J. W., Liu, W., Dunn, T. A., Luo, J., Loza, M. J., ... Chang, B. L. (2009). Genetic and epigenetic inactivation of TNFRSFI0C in human prostate cancer. Prostate, 69(3), 327-335. https://doi.org/10.1002/pros.20882

Genetic and epigenetic inactivation of TNFRSFI0C in human prostate cancer. / Cheng, Yu; Kim, Jin Woo; Liu, Wennuan; Dunn, Thomas A.; Luo, Jun; Loza, Matthew J.; Kim, Seong Tae; Zheng, Siqun Lilly; Xu, Jianfeng; Isaacs, William B; Chang, Bao Li.

In: Prostate, Vol. 69, No. 3, 15.02.2009, p. 327-335.

Research output: Contribution to journalArticle

Cheng, Y, Kim, JW, Liu, W, Dunn, TA, Luo, J, Loza, MJ, Kim, ST, Zheng, SL, Xu, J, Isaacs, WB & Chang, BL 2009, 'Genetic and epigenetic inactivation of TNFRSFI0C in human prostate cancer', Prostate, vol. 69, no. 3, pp. 327-335. https://doi.org/10.1002/pros.20882
Cheng, Yu ; Kim, Jin Woo ; Liu, Wennuan ; Dunn, Thomas A. ; Luo, Jun ; Loza, Matthew J. ; Kim, Seong Tae ; Zheng, Siqun Lilly ; Xu, Jianfeng ; Isaacs, William B ; Chang, Bao Li. / Genetic and epigenetic inactivation of TNFRSFI0C in human prostate cancer. In: Prostate. 2009 ; Vol. 69, No. 3. pp. 327-335.
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abstract = "BACKGROUND. TNFRSF10C, is located on 8p21.3, one of the most frequently deleted loci in the genome of prostate cancer (PCa). Hypermethylation of TNFRSF10C promoter CpG island (CGI) had been reported in many tumors including PCa. However, the interplay between somatic deletion and promoter hypermethylation of TNFRSF10C on PCa development has not been investigated. METHODS. Methylation status of promoter CGI and deletion status of the TNFRSF10C locus was investigated by bisulfite sequencing and Affymetrix SNP array, respectively, in 59 pairs of PCa tumor and matched normal samples with three PCa cell lines. TNFRSF10C gene expression changes in relation to cancer-associated genetic/epigenetic changes in clinical specimens, and change of TNFRSF10C expression before and after 5-aza-20-deoxycytidine treatment in the PC3 PCa cell line was assessed by real-time RT-PCR. RESULTS. We found that TNFRSF10C promoter CGI was differentially methylated in 46 of 59 primary cancers (78.0{\%}). Hemizygous deletion at TNFRSF10C was found in 44 of the 59 prostate tumors (74.5{\%}). Interestingly, in 94.9{\%} of the tumors (56 out of 59), TNFRSF10C was either hemizygously deleted or its promoter CGI hypermethylated. Deletion and/or methylation of the TNFRSF10C gene were correlated with decreased mRNA expression of the gene in clinical specimens. Demethylation of the TNFRSF10C promoter CGI was accompanied by transcriptional re-activation of TNFRSF10C in the PCa cell line PC3. CONCLUSION. We found a notably high frequency of promoter CGI methylation and deletion of TNFRSF10C in PCa tissues. Our results indicated that inactivation of TNFRSF10C by chromosomal deletion and promoter methylation may play an important role in PCa development.",
keywords = "CpG islands, Promoter methylation, Somatic copy number alterations",
author = "Yu Cheng and Kim, {Jin Woo} and Wennuan Liu and Dunn, {Thomas A.} and Jun Luo and Loza, {Matthew J.} and Kim, {Seong Tae} and Zheng, {Siqun Lilly} and Jianfeng Xu and Isaacs, {William B} and Chang, {Bao Li}",
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T1 - Genetic and epigenetic inactivation of TNFRSFI0C in human prostate cancer

AU - Cheng, Yu

AU - Kim, Jin Woo

AU - Liu, Wennuan

AU - Dunn, Thomas A.

AU - Luo, Jun

AU - Loza, Matthew J.

AU - Kim, Seong Tae

AU - Zheng, Siqun Lilly

AU - Xu, Jianfeng

AU - Isaacs, William B

AU - Chang, Bao Li

PY - 2009/2/15

Y1 - 2009/2/15

N2 - BACKGROUND. TNFRSF10C, is located on 8p21.3, one of the most frequently deleted loci in the genome of prostate cancer (PCa). Hypermethylation of TNFRSF10C promoter CpG island (CGI) had been reported in many tumors including PCa. However, the interplay between somatic deletion and promoter hypermethylation of TNFRSF10C on PCa development has not been investigated. METHODS. Methylation status of promoter CGI and deletion status of the TNFRSF10C locus was investigated by bisulfite sequencing and Affymetrix SNP array, respectively, in 59 pairs of PCa tumor and matched normal samples with three PCa cell lines. TNFRSF10C gene expression changes in relation to cancer-associated genetic/epigenetic changes in clinical specimens, and change of TNFRSF10C expression before and after 5-aza-20-deoxycytidine treatment in the PC3 PCa cell line was assessed by real-time RT-PCR. RESULTS. We found that TNFRSF10C promoter CGI was differentially methylated in 46 of 59 primary cancers (78.0%). Hemizygous deletion at TNFRSF10C was found in 44 of the 59 prostate tumors (74.5%). Interestingly, in 94.9% of the tumors (56 out of 59), TNFRSF10C was either hemizygously deleted or its promoter CGI hypermethylated. Deletion and/or methylation of the TNFRSF10C gene were correlated with decreased mRNA expression of the gene in clinical specimens. Demethylation of the TNFRSF10C promoter CGI was accompanied by transcriptional re-activation of TNFRSF10C in the PCa cell line PC3. CONCLUSION. We found a notably high frequency of promoter CGI methylation and deletion of TNFRSF10C in PCa tissues. Our results indicated that inactivation of TNFRSF10C by chromosomal deletion and promoter methylation may play an important role in PCa development.

AB - BACKGROUND. TNFRSF10C, is located on 8p21.3, one of the most frequently deleted loci in the genome of prostate cancer (PCa). Hypermethylation of TNFRSF10C promoter CpG island (CGI) had been reported in many tumors including PCa. However, the interplay between somatic deletion and promoter hypermethylation of TNFRSF10C on PCa development has not been investigated. METHODS. Methylation status of promoter CGI and deletion status of the TNFRSF10C locus was investigated by bisulfite sequencing and Affymetrix SNP array, respectively, in 59 pairs of PCa tumor and matched normal samples with three PCa cell lines. TNFRSF10C gene expression changes in relation to cancer-associated genetic/epigenetic changes in clinical specimens, and change of TNFRSF10C expression before and after 5-aza-20-deoxycytidine treatment in the PC3 PCa cell line was assessed by real-time RT-PCR. RESULTS. We found that TNFRSF10C promoter CGI was differentially methylated in 46 of 59 primary cancers (78.0%). Hemizygous deletion at TNFRSF10C was found in 44 of the 59 prostate tumors (74.5%). Interestingly, in 94.9% of the tumors (56 out of 59), TNFRSF10C was either hemizygously deleted or its promoter CGI hypermethylated. Deletion and/or methylation of the TNFRSF10C gene were correlated with decreased mRNA expression of the gene in clinical specimens. Demethylation of the TNFRSF10C promoter CGI was accompanied by transcriptional re-activation of TNFRSF10C in the PCa cell line PC3. CONCLUSION. We found a notably high frequency of promoter CGI methylation and deletion of TNFRSF10C in PCa tissues. Our results indicated that inactivation of TNFRSF10C by chromosomal deletion and promoter methylation may play an important role in PCa development.

KW - CpG islands

KW - Promoter methylation

KW - Somatic copy number alterations

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