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Combined RASSF1A and RASSF2A Promoter Methylation Analysis as Diagnostic Biomarker for Bladder Cancer.

Meng W, Huebner A, Shabsigh A, Chakravarti A, Lautenschlaeger T - Mol Biol Int (2012)

Bottom Line: Promoter hypermethylation, a widely studied epigenetic event known to influence gene expression levels, has been proposed as a potential biomarker in multiple types of cancer.Clinical diagnostic biomarkers are needed for reliable prediction of bladder cancer recurrence.Results showed that 73% (30/41) of transitional cell carcinoma, 100% (3/3) of squamous cell carcinoma, and 100% (4/4) of small cell carcinoma demonstrated promoter methylation of the RASSF1A or RASSF2A gene, but only 6% (1/16) of normal tissues had promoter methylation of RASSF genes.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiation Oncology, The Ohio State University, Columbus, OH 43210, USA.

ABSTRACT
Promoter hypermethylation, a widely studied epigenetic event known to influence gene expression levels, has been proposed as a potential biomarker in multiple types of cancer. Clinical diagnostic biomarkers are needed for reliable prediction of bladder cancer recurrence. In this paper, DNA promoter methylation of five C-terminal Ras-association family members (RASSF1A, RASSF2A, RASSF4, RASSF5, and RASSF6) was studied in 64 formalin-fixed paraffin-embedded (FFPE) bladder cancer and normal adjacent tissues using methylation-specific high-resolution melting (MS-HRM) analysis. Results showed that 73% (30/41) of transitional cell carcinoma, 100% (3/3) of squamous cell carcinoma, and 100% (4/4) of small cell carcinoma demonstrated promoter methylation of the RASSF1A or RASSF2A gene, but only 6% (1/16) of normal tissues had promoter methylation of RASSF genes. Testing positive for hypermethylation of RASSF1A or RASSF2A promoter provided 77% sensitivity and 94% specificity for identification of cancer tissues with an area under the curve of 0.854, suggesting that promoter methylation analysis of RASSF1A and RASSF2A genes has potential for use as a recurrence biomarker for bladder cancer patients.

No MeSH data available.


Related in: MedlinePlus

RASSF1A and RASSF2A methylation profiles of different histology. RASSF1A was methylated in 68% (28/41) of transitional cell carcinoma samples, in 100% (4/4) of small cell carcinoma and in 67% (2/3) of squamous cell carcinoma. RASSF2A was methylated in 7% (3/41) of transitional cell carcinoma samples, in 0% (0/4) of small cell carcinoma, and in 33% (1/3) of squamous cell carcinoma.
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fig3: RASSF1A and RASSF2A methylation profiles of different histology. RASSF1A was methylated in 68% (28/41) of transitional cell carcinoma samples, in 100% (4/4) of small cell carcinoma and in 67% (2/3) of squamous cell carcinoma. RASSF2A was methylated in 7% (3/41) of transitional cell carcinoma samples, in 0% (0/4) of small cell carcinoma, and in 33% (1/3) of squamous cell carcinoma.

Mentions: Patient characteristics are summarized in Table 1. 41 patients had tumors with transitional cell carcinoma features 4 with small cell carcinoma, and 3 with squamous cell carcinoma. RASSF1A was methylated in 68% (28/41) and RASSF2A in 7% (3/41) of transitional cell carcinoma samples. Only one sample had methylation of both the RASSF1A and RASSF2A promoters. RASSF1A was methylated in 100% (4/4) and RASSF2A in 0% (0/4) of small cell carcinoma. RASSF1A was methylated in 67% (2/3) and RASSF2A in 33% (1/3) of squamous cell carcinoma (Figure 3). The frequency of RASSF1 and RASSF2 promoter methylation together showed no significant difference with histology in our study (P = 0.295).


Combined RASSF1A and RASSF2A Promoter Methylation Analysis as Diagnostic Biomarker for Bladder Cancer.

Meng W, Huebner A, Shabsigh A, Chakravarti A, Lautenschlaeger T - Mol Biol Int (2012)

RASSF1A and RASSF2A methylation profiles of different histology. RASSF1A was methylated in 68% (28/41) of transitional cell carcinoma samples, in 100% (4/4) of small cell carcinoma and in 67% (2/3) of squamous cell carcinoma. RASSF2A was methylated in 7% (3/41) of transitional cell carcinoma samples, in 0% (0/4) of small cell carcinoma, and in 33% (1/3) of squamous cell carcinoma.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3316979&req=5

fig3: RASSF1A and RASSF2A methylation profiles of different histology. RASSF1A was methylated in 68% (28/41) of transitional cell carcinoma samples, in 100% (4/4) of small cell carcinoma and in 67% (2/3) of squamous cell carcinoma. RASSF2A was methylated in 7% (3/41) of transitional cell carcinoma samples, in 0% (0/4) of small cell carcinoma, and in 33% (1/3) of squamous cell carcinoma.
Mentions: Patient characteristics are summarized in Table 1. 41 patients had tumors with transitional cell carcinoma features 4 with small cell carcinoma, and 3 with squamous cell carcinoma. RASSF1A was methylated in 68% (28/41) and RASSF2A in 7% (3/41) of transitional cell carcinoma samples. Only one sample had methylation of both the RASSF1A and RASSF2A promoters. RASSF1A was methylated in 100% (4/4) and RASSF2A in 0% (0/4) of small cell carcinoma. RASSF1A was methylated in 67% (2/3) and RASSF2A in 33% (1/3) of squamous cell carcinoma (Figure 3). The frequency of RASSF1 and RASSF2 promoter methylation together showed no significant difference with histology in our study (P = 0.295).

Bottom Line: Promoter hypermethylation, a widely studied epigenetic event known to influence gene expression levels, has been proposed as a potential biomarker in multiple types of cancer.Clinical diagnostic biomarkers are needed for reliable prediction of bladder cancer recurrence.Results showed that 73% (30/41) of transitional cell carcinoma, 100% (3/3) of squamous cell carcinoma, and 100% (4/4) of small cell carcinoma demonstrated promoter methylation of the RASSF1A or RASSF2A gene, but only 6% (1/16) of normal tissues had promoter methylation of RASSF genes.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiation Oncology, The Ohio State University, Columbus, OH 43210, USA.

ABSTRACT
Promoter hypermethylation, a widely studied epigenetic event known to influence gene expression levels, has been proposed as a potential biomarker in multiple types of cancer. Clinical diagnostic biomarkers are needed for reliable prediction of bladder cancer recurrence. In this paper, DNA promoter methylation of five C-terminal Ras-association family members (RASSF1A, RASSF2A, RASSF4, RASSF5, and RASSF6) was studied in 64 formalin-fixed paraffin-embedded (FFPE) bladder cancer and normal adjacent tissues using methylation-specific high-resolution melting (MS-HRM) analysis. Results showed that 73% (30/41) of transitional cell carcinoma, 100% (3/3) of squamous cell carcinoma, and 100% (4/4) of small cell carcinoma demonstrated promoter methylation of the RASSF1A or RASSF2A gene, but only 6% (1/16) of normal tissues had promoter methylation of RASSF genes. Testing positive for hypermethylation of RASSF1A or RASSF2A promoter provided 77% sensitivity and 94% specificity for identification of cancer tissues with an area under the curve of 0.854, suggesting that promoter methylation analysis of RASSF1A and RASSF2A genes has potential for use as a recurrence biomarker for bladder cancer patients.

No MeSH data available.


Related in: MedlinePlus