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Epigenetic Molecular Markers: A New Tool For Segregating Aggressive From
Indolent Prostate Cancers.
(June 2006)
Susan
Cottrell, senior scientist at the Seattle branch of the biotech company,
EPIGENOMICS, presented her group's findings at the 2006 AACR Symposium
showing that quantitative real-time PCR analysis of the methylation status
of five molecular markers yielded valid predictions of prostate cancer
aggressiveness. Also studied was a sixth marker, PITX2, also prognostic
for breast cancer outcome, and the results were impressive for predicting
outcome for prostate cancer: "The methylation of PITX2 provided
information beyond what is already provided by traditional prognostic
indicators such as Gleason analysis, pre-surgical PSA, staging, and a
nomogram". "PITX2 positive patients have a 5-fold higher risk for PSA
recurrence within 10 years."
Their
study was performed on 605 formalin-fixed, paraffin-embedded RP specimens,
and analyzed the extent to which the candidate markers were aberrantly
methylated, and correlated the results with post surgical outcomes. The
addition of methyl groups to cytosine/guanine dinucleotides, usually
targeted to the promoter region of a gene, is an important epigenetic
mechanism that impedes the normal transcription process resulting in
alteration of gene expression and cellular behavior.
"Hypermethylation
of all six markers were correlated with poor survival, but three markers
(PITX2 [p=0.00017], GPR7 [p=0.0096], and an EST ['expressed sequence tag']
on chromosome 3 [p=0.035] were statistically significant when the median
methylation level was used for cut-off", showing "strong separation of
good and poor prognostic groups".
It is
anticipated that after further validation this test will become
commercially available and contribute useful additional information for
treatment selection. Additionally, "Prostatectomy patients testing
positive for hypermethylation of these markers would be an ideal sub-group
for clinical trials on the efficacy of early adjuvant therapy".
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