Genetic and epigenetic inactivation of LPL gene in human prostate cancer

Jin Woo Kim, Yu Cheng, Wennuan Liu, Tao Li, S Yegnasubramanian, Siqun L. Zheng, Jianfeng Xu, William B Isaacs, Bao Li Chang

Research output: Contribution to journalArticle

Abstract

Lipoprotein lipase (LPL) is in chromosome 8p22, site of one of the most common somatic deletions in prostate tumors. Additionally, a CpG island (CGI) was identified in the LPL promoter region. To test the hypothesis that LPL is a tumor suppressor gene, which is inactivated by somatic deletion and hypermethylation in prostate cancer, we evaluated somatic DNA deletion and methylation status at LPL in 56 pairs of DNA samples isolated from prostate cancer tissues and matching normal controls and 11 prostate cell lines. We found that the DNA in 21 of 56 primary cancers (38%) was methylated in the LPL promoter CGI, whereas no methylation was detected in any normal samples. In addition, we found a hemizygous deletion at LPL in 38 of the 56 tumors (68%). When the results of deletion and methylation were considered together, we found LPL promoter CGI methylation occurred in 45% of LPL deleted tumors and in 22% of LPL retained tumors. Within several clinical characteristics tested, the preoperative PSA levels were found to be significantly higher in subjects with LPL promoter CGI methylation compared with subjects without LPL promoter methylation (p = 0.0012). Additionally, demethylation of the LPL promoter CGI was accompanied by transcriptional reactivation of LPL in the prostate cancer cell lines DU145 and PC3. In summary, we report a novel finding that the LPL gene is commonly methylated in prostate tumors, and our results suggest that biallelic inactivation of LPL by chromosomal deletion and promoter hypermethylation may play a role in human prostate cancer.

Original languageEnglish (US)
Pages (from-to)734-738
Number of pages5
JournalInternational Journal of Cancer
Volume124
Issue number3
DOIs
StatePublished - Feb 1 2009

Fingerprint

Lipoprotein Lipase
Epigenomics
Prostatic Neoplasms
Genes
CpG Islands
Methylation
Prostate
Neoplasms
Cell Line
DNA
DNA Methylation
Tumor Suppressor Genes
Genetic Promoter Regions

Keywords

  • Biallelic inactivation
  • LPL
  • Promoter methylation
  • Prostate cancer
  • Somatic deletion

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Genetic and epigenetic inactivation of LPL gene in human prostate cancer. / Kim, Jin Woo; Cheng, Yu; Liu, Wennuan; Li, Tao; Yegnasubramanian, S; Zheng, Siqun L.; Xu, Jianfeng; Isaacs, William B; Chang, Bao Li.

In: International Journal of Cancer, Vol. 124, No. 3, 01.02.2009, p. 734-738.

Research output: Contribution to journalArticle

Kim, Jin Woo ; Cheng, Yu ; Liu, Wennuan ; Li, Tao ; Yegnasubramanian, S ; Zheng, Siqun L. ; Xu, Jianfeng ; Isaacs, William B ; Chang, Bao Li. / Genetic and epigenetic inactivation of LPL gene in human prostate cancer. In: International Journal of Cancer. 2009 ; Vol. 124, No. 3. pp. 734-738.
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abstract = "Lipoprotein lipase (LPL) is in chromosome 8p22, site of one of the most common somatic deletions in prostate tumors. Additionally, a CpG island (CGI) was identified in the LPL promoter region. To test the hypothesis that LPL is a tumor suppressor gene, which is inactivated by somatic deletion and hypermethylation in prostate cancer, we evaluated somatic DNA deletion and methylation status at LPL in 56 pairs of DNA samples isolated from prostate cancer tissues and matching normal controls and 11 prostate cell lines. We found that the DNA in 21 of 56 primary cancers (38{\%}) was methylated in the LPL promoter CGI, whereas no methylation was detected in any normal samples. In addition, we found a hemizygous deletion at LPL in 38 of the 56 tumors (68{\%}). When the results of deletion and methylation were considered together, we found LPL promoter CGI methylation occurred in 45{\%} of LPL deleted tumors and in 22{\%} of LPL retained tumors. Within several clinical characteristics tested, the preoperative PSA levels were found to be significantly higher in subjects with LPL promoter CGI methylation compared with subjects without LPL promoter methylation (p = 0.0012). Additionally, demethylation of the LPL promoter CGI was accompanied by transcriptional reactivation of LPL in the prostate cancer cell lines DU145 and PC3. In summary, we report a novel finding that the LPL gene is commonly methylated in prostate tumors, and our results suggest that biallelic inactivation of LPL by chromosomal deletion and promoter hypermethylation may play a role in human prostate cancer.",
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AU - Zheng, Siqun L.

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AU - Chang, Bao Li

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AB - Lipoprotein lipase (LPL) is in chromosome 8p22, site of one of the most common somatic deletions in prostate tumors. Additionally, a CpG island (CGI) was identified in the LPL promoter region. To test the hypothesis that LPL is a tumor suppressor gene, which is inactivated by somatic deletion and hypermethylation in prostate cancer, we evaluated somatic DNA deletion and methylation status at LPL in 56 pairs of DNA samples isolated from prostate cancer tissues and matching normal controls and 11 prostate cell lines. We found that the DNA in 21 of 56 primary cancers (38%) was methylated in the LPL promoter CGI, whereas no methylation was detected in any normal samples. In addition, we found a hemizygous deletion at LPL in 38 of the 56 tumors (68%). When the results of deletion and methylation were considered together, we found LPL promoter CGI methylation occurred in 45% of LPL deleted tumors and in 22% of LPL retained tumors. Within several clinical characteristics tested, the preoperative PSA levels were found to be significantly higher in subjects with LPL promoter CGI methylation compared with subjects without LPL promoter methylation (p = 0.0012). Additionally, demethylation of the LPL promoter CGI was accompanied by transcriptional reactivation of LPL in the prostate cancer cell lines DU145 and PC3. In summary, we report a novel finding that the LPL gene is commonly methylated in prostate tumors, and our results suggest that biallelic inactivation of LPL by chromosomal deletion and promoter hypermethylation may play a role in human prostate cancer.

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