Hypermethylation of AP-2alpha as a Prognostic Marker for DCIS
Annual rept. 19 Apr 2005-18 Apr 2006
JOHNS HOPKINS UNIV BALTIMORE MD SCHOOL OF MEDICINE
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Fifteen to 20 of women with initial DCIS subsequently manifest invasive breast carcinoma. At present, there is no real means to predict which patients will undergo this disease progression and recurrence. The purpose of this IDEA, DOD award is to determine whether hypermethylation of the AP-2alpha, and other genes, may identify those DCIS lesions at high risk for recurrence as invasive breast carcinoma. The idea was based on a small initial study 15 samples where we found only 20 of DCIS samples, versus 70 of invasive tumors, had AP-2alpha hypermethylation. Our first chief aim was to verify these findings and identify other genes which might also prove useful as prognostic markers. During the past year, we have accomplished this goal by deriving a panel of 5 genes, including AP-2alpha, any two of which when hypermethylated in DCIS, preliminarily tracks with patients who develop recurrent disease. Each marker, in the main, has a much higher incidence of hypermethylation in invasive breast cancer versus DCIS. We are now ready, in the definitive case control study with UCSF, to test this panel of genes for its efficacy in predicting cases of DCIS which are likely to recur. We have also used the panel in a study with Steve Belinsky and are awaiting breaking of the code for longitudinal five year follow up to see how the results track with recurrent disease.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research
- Organic Chemistry