In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 6_suppl ( 2013-02-20), p. 80-80
Abstract:
80 Background: The characterization of actionable mutations is a prerequisite for the development of individualized, targeted therapy. We sought to characterize the prevalence of potentially therapeutically actionable mutations in patients with high risk prostate cancer. Methods: 48 samples of formalin fixed paraffin embedded prostatectomy tissue from a neoadjuvant chemotherapy trial (Garzotto M, Cancer 2010 Apr 1;116(7):1699-708) were analyzed. DNA was extracted from microdissected tumor. Tumor DNA was analyzed for 643 common solid tumor point mutations in 53 genes using mass spectroscopy based sequencing (Sequenom MassArray). Low level mutations were validated using ion chip pH based sequencing (Ion Torrent). In addition, PTEN loss and ERG translocations were examined using immunohistochemistry in associated tissue microarrays. Correlation with relapse during 5 years of follow-up was examined in exploratory analyses of the potential clinical relevance of the genetic alterations examined. Results: Of the 40 tumors evaluable for mutations, 10% had point mutations in potentially actionable cancer genes. Of the 45 tumors evaluable for IHC, 36% had PTEN loss (6% with a heterogenous pattern) and 40% had ERG rearrangement (2% with heterogeneous pattern). Individual mutations were not frequent enough to determine associations with progression. Using Kaplan-Meier analysis with a log-rank test, the 16 patients who had PTEN loss had a significantly shorter median progression free survival, 19 vs. 106 months (p = .01). Conclusions: This study confirms that point mutations in the most common cancer regulatory genes in prostate cancer are rare. However, the PIK3CA/AKT pathway was mutated in 10% of our samples. While point mutations alone did not have a statistically significant effect on relapse, PTEN loss was associated with an increased relapse in high risk prostate cancer treated with chemotherapy followed by surgery. It is yet unclear if the 16 weeks of chemotherapy played a role in selecting for tumors with these biologic features, and this will therefore be the subject of future investigations. [Table: see text]
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2013.31.6_suppl.80
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2013
detail.hit.zdb_id:
2005181-5
Permalink
