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Promoter Methylation in Prostate Cancer and its Application for the Early Detection of Prostate Cancer Using Serum and Urine Samples.

Ahmed H - Biomark Cancer (2010)

Bottom Line: Combined with the digital rectal examination, the PSA test has been widely used to detect prostate cancer.But, the PSA screening method for early detection of prostate cancer is not reliable due to the high prevalence of false positive and false negative results.This review discusses DNA methylation of several gene promoters during prostate carcinogenesis and evaluates the usefulness of monitoring methylated DNA sequences, such as GSTP1, RASSF1A, RARβ2 and galectin-3, for early detection of prostate cancer in tissue biopsies, serum and urine.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, Program in Oncology, Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

ABSTRACT
Prostate cancer is the second most common cancer and the second leading cause of cancer death in men. However, prostate cancer can be effectively treated and cured, if it is diagnosed in its early stages when the tumor is still confined to the prostate. Combined with the digital rectal examination, the PSA test has been widely used to detect prostate cancer. But, the PSA screening method for early detection of prostate cancer is not reliable due to the high prevalence of false positive and false negative results. Epigenetic alterations including hypermethylation of gene promoters are believed to be the early events in neoplastic progression and thus these methylated genes can serve as biomarkers for the detection of cancer from clinical specimens. This review discusses DNA methylation of several gene promoters during prostate carcinogenesis and evaluates the usefulness of monitoring methylated DNA sequences, such as GSTP1, RASSF1A, RARβ2 and galectin-3, for early detection of prostate cancer in tissue biopsies, serum and urine.

No MeSH data available.


Related in: MedlinePlus

Schematic representation of MS-PCR. In normal and BPH prostate tissues, the gal3 promoter is unmethylated, whereas in stage I and II, it is methylated heavily. However, gal3 promoter is lightly methylated in stage III and IV. Stage-specific cytosine methylation of the gal3 promoter enabled the development of MS-PCR for the detection of stage I and II PCa.
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f3-bic-2-2010-017: Schematic representation of MS-PCR. In normal and BPH prostate tissues, the gal3 promoter is unmethylated, whereas in stage I and II, it is methylated heavily. However, gal3 promoter is lightly methylated in stage III and IV. Stage-specific cytosine methylation of the gal3 promoter enabled the development of MS-PCR for the detection of stage I and II PCa.

Mentions: The finding that the gal3 gene promoter is completely methylated in stage I and II PCa makes the gal3 gene (LGALS3) an ideal candidate for developing a methylation-specific PCR (MS-PCR) assay for early diagnosis of PCa.126,127 Because stage I and II tumors are still confined to the prostate gland, identification of these stages is very important for effective intervention and cure. As the gal3 promoter is also methylated in stage III and IV, but only lightly and only between nt positions −112 to −252, we designed primers covering −9 nt to +64 nt to specifically detect stage I and II PCa (Fig. 3).127 Of 34 tissues (5 normal, 2 BPH, 11 stage I, 7 stage II, 7 stage III, and 2 stage IV) tested, gal3 MS-PCR was positive with all stage I and II tumor samples (100% sensitive) on a semi-quantitative MS-PCR assay.127 As expected, the gal3 MS-PCR was negative for normal, BPH, stage III (except one), and stage IV samples. In order to detect stage III and IV PCa samples along with the stage I and II, another assay based on GSTP1 promoter methylation has been added with the gal3 MS-PCR. The combined MS-PCR assay (gal3 and GSTP1) detected 26 out of 27 prostate cancer tissues.127


Promoter Methylation in Prostate Cancer and its Application for the Early Detection of Prostate Cancer Using Serum and Urine Samples.

Ahmed H - Biomark Cancer (2010)

Schematic representation of MS-PCR. In normal and BPH prostate tissues, the gal3 promoter is unmethylated, whereas in stage I and II, it is methylated heavily. However, gal3 promoter is lightly methylated in stage III and IV. Stage-specific cytosine methylation of the gal3 promoter enabled the development of MS-PCR for the detection of stage I and II PCa.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2908742&req=5

f3-bic-2-2010-017: Schematic representation of MS-PCR. In normal and BPH prostate tissues, the gal3 promoter is unmethylated, whereas in stage I and II, it is methylated heavily. However, gal3 promoter is lightly methylated in stage III and IV. Stage-specific cytosine methylation of the gal3 promoter enabled the development of MS-PCR for the detection of stage I and II PCa.
Mentions: The finding that the gal3 gene promoter is completely methylated in stage I and II PCa makes the gal3 gene (LGALS3) an ideal candidate for developing a methylation-specific PCR (MS-PCR) assay for early diagnosis of PCa.126,127 Because stage I and II tumors are still confined to the prostate gland, identification of these stages is very important for effective intervention and cure. As the gal3 promoter is also methylated in stage III and IV, but only lightly and only between nt positions −112 to −252, we designed primers covering −9 nt to +64 nt to specifically detect stage I and II PCa (Fig. 3).127 Of 34 tissues (5 normal, 2 BPH, 11 stage I, 7 stage II, 7 stage III, and 2 stage IV) tested, gal3 MS-PCR was positive with all stage I and II tumor samples (100% sensitive) on a semi-quantitative MS-PCR assay.127 As expected, the gal3 MS-PCR was negative for normal, BPH, stage III (except one), and stage IV samples. In order to detect stage III and IV PCa samples along with the stage I and II, another assay based on GSTP1 promoter methylation has been added with the gal3 MS-PCR. The combined MS-PCR assay (gal3 and GSTP1) detected 26 out of 27 prostate cancer tissues.127

Bottom Line: Combined with the digital rectal examination, the PSA test has been widely used to detect prostate cancer.But, the PSA screening method for early detection of prostate cancer is not reliable due to the high prevalence of false positive and false negative results.This review discusses DNA methylation of several gene promoters during prostate carcinogenesis and evaluates the usefulness of monitoring methylated DNA sequences, such as GSTP1, RASSF1A, RARβ2 and galectin-3, for early detection of prostate cancer in tissue biopsies, serum and urine.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, Program in Oncology, Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

ABSTRACT
Prostate cancer is the second most common cancer and the second leading cause of cancer death in men. However, prostate cancer can be effectively treated and cured, if it is diagnosed in its early stages when the tumor is still confined to the prostate. Combined with the digital rectal examination, the PSA test has been widely used to detect prostate cancer. But, the PSA screening method for early detection of prostate cancer is not reliable due to the high prevalence of false positive and false negative results. Epigenetic alterations including hypermethylation of gene promoters are believed to be the early events in neoplastic progression and thus these methylated genes can serve as biomarkers for the detection of cancer from clinical specimens. This review discusses DNA methylation of several gene promoters during prostate carcinogenesis and evaluates the usefulness of monitoring methylated DNA sequences, such as GSTP1, RASSF1A, RARβ2 and galectin-3, for early detection of prostate cancer in tissue biopsies, serum and urine.

No MeSH data available.


Related in: MedlinePlus