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A tissue biopsy-based epigenetic multiplex PCR assay for prostate cancer detection

Leander Van Neste UGent, Joseph Bigley, Adam Toll, Gaëtan Otto, James Clark, Paul Delrée, Wim Van Criekinge UGent and Jonathan I Epstein (2012) BMC UROLOGY. 12.
abstract
Background: PSA-directed prostate cancer screening leads to a high rate of false positive identifications and an unnecessary biopsy burden. Epigenetic biomarkers have proven useful, exhibiting frequent and abundant inactivation of tumor suppressor genes through such mechanisms. An epigenetic, multiplex PCR test for prostate cancer diagnosis could provide physicians with better tools to help their patients. Biomarkers like GSTP1, APC and RASSF1 have demonstrated involvement with prostate cancer, with the latter two genes playing prominent roles in the field effect. The epigenetic states of these genes can be used to assess the likelihood of cancer presence or absence. Results: An initial test cohort of 30 prostate cancer-positive samples and 12 cancer-negative samples was used as basis for the development and optimization of an epigenetic multiplex assay based on the GSTP1, APC and RASSF1 genes, using methylation specific PCR (MSP). The effect of prostate needle core biopsy sample volume and age of formalin-fixed paraffin-embedded (FFPE) samples was evaluated on an independent follow-up cohort of 51 cancer-positive patients. Multiplexing affects copy number calculations in a consistent way per assay. Methylation ratios are therefore altered compared to the respective singleplex assays, but the correlation with patient outcome remains equivalent. In addition, tissue-biopsy samples as small as 20 mu m can be used to detect methylation in a reliable manner. The age of FFPE-samples does have a negative impact on DNA quality and quantity. Conclusions: The developed multiplex assay appears functionally similar to individual singleplex assays, with the benefit of lower tissue requirements, lower cost and decreased signal variation. This assay can be applied to small biopsy specimens, down to 20 microns, widening clinical applicability. Increasing the sample volume can compensate the loss of DNA quality and quantity in older samples.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
PROMOTER METHYLATION, CPG ISLANDS, SERVICES-TASK-FORCE, MULTICENTER CLINICAL-TRIAL, MSP, Singleplex, Multiplex, Diagnosis, Prostate cancer, Epigenetics, Methylation, RASSF1, GSTP1, APC, GENE, ANTIGEN, MEN, HYPERMETHYLATION, MORTALITY, DIAGNOSIS
journal title
BMC UROLOGY
BMC Urol.
volume
12
article number
16
pages
8 pages
Web of Science type
Article
Web of Science id
000313240900001
JCR category
UROLOGY & NEPHROLOGY
JCR impact factor
1.694 (2012)
JCR rank
37/73 (2012)
JCR quartile
3 (2012)
ISSN
1471-2490
DOI
10.1186/1471-2490-12-16
language
English
UGent publication?
no
classification
A1
copyright statement
I have retained and own the full copyright for this publication
id
3168785
handle
http://hdl.handle.net/1854/LU-3168785
date created
2013-03-19 14:48:37
date last changed
2017-02-22 14:37:02
@article{3168785,
  abstract     = {Background: PSA-directed prostate cancer screening leads to a high rate of false positive identifications and an unnecessary biopsy burden. Epigenetic biomarkers have proven useful, exhibiting frequent and abundant inactivation of tumor suppressor genes through such mechanisms. An epigenetic, multiplex PCR test for prostate cancer diagnosis could provide physicians with better tools to help their patients. Biomarkers like GSTP1, APC and RASSF1 have demonstrated involvement with prostate cancer, with the latter two genes playing prominent roles in the field effect. The epigenetic states of these genes can be used to assess the likelihood of cancer presence or absence. 
Results: An initial test cohort of 30 prostate cancer-positive samples and 12 cancer-negative samples was used as basis for the development and optimization of an epigenetic multiplex assay based on the GSTP1, APC and RASSF1 genes, using methylation specific PCR (MSP). The effect of prostate needle core biopsy sample volume and age of formalin-fixed paraffin-embedded (FFPE) samples was evaluated on an independent follow-up cohort of 51 cancer-positive patients. Multiplexing affects copy number calculations in a consistent way per assay. Methylation ratios are therefore altered compared to the respective singleplex assays, but the correlation with patient outcome remains equivalent. In addition, tissue-biopsy samples as small as 20 mu m can be used to detect methylation in a reliable manner. The age of FFPE-samples does have a negative impact on DNA quality and quantity. 
Conclusions: The developed multiplex assay appears functionally similar to individual singleplex assays, with the benefit of lower tissue requirements, lower cost and decreased signal variation. This assay can be applied to small biopsy specimens, down to 20 microns, widening clinical applicability. Increasing the sample volume can compensate the loss of DNA quality and quantity in older samples.},
  articleno    = {16},
  author       = {Van Neste, Leander and Bigley, Joseph and Toll, Adam and Otto, Ga{\"e}tan and Clark, James and Delr{\'e}e, Paul and Van Criekinge, Wim and Epstein, Jonathan I},
  issn         = {1471-2490},
  journal      = {BMC UROLOGY},
  keyword      = {PROMOTER METHYLATION,CPG ISLANDS,SERVICES-TASK-FORCE,MULTICENTER CLINICAL-TRIAL,MSP,Singleplex,Multiplex,Diagnosis,Prostate cancer,Epigenetics,Methylation,RASSF1,GSTP1,APC,GENE,ANTIGEN,MEN,HYPERMETHYLATION,MORTALITY,DIAGNOSIS},
  language     = {eng},
  pages        = {8},
  title        = {A tissue biopsy-based epigenetic multiplex PCR assay for prostate cancer detection},
  url          = {http://dx.doi.org/10.1186/1471-2490-12-16},
  volume       = {12},
  year         = {2012},
}

Chicago
Van Neste, Leander, Joseph Bigley, Adam Toll, Gaëtan Otto, James Clark, Paul Delrée, Wim Van Criekinge, and Jonathan I Epstein. 2012. “A Tissue Biopsy-based Epigenetic Multiplex PCR Assay for Prostate Cancer Detection.” Bmc Urology 12.
APA
Van Neste, L., Bigley, J., Toll, A., Otto, G., Clark, J., Delrée, P., Van Criekinge, W., et al. (2012). A tissue biopsy-based epigenetic multiplex PCR assay for prostate cancer detection. BMC UROLOGY, 12.
Vancouver
1.
Van Neste L, Bigley J, Toll A, Otto G, Clark J, Delrée P, et al. A tissue biopsy-based epigenetic multiplex PCR assay for prostate cancer detection. BMC UROLOGY. 2012;12.
MLA
Van Neste, Leander, Joseph Bigley, Adam Toll, et al. “A Tissue Biopsy-based Epigenetic Multiplex PCR Assay for Prostate Cancer Detection.” BMC UROLOGY 12 (2012): n. pag. Print.