In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 7_suppl ( 2015-03-01), p. 244-244
Abstract:
244 Background: Personalizing CRPC therapy is desirable but difficult as biomarkers that have predictive value other than AR-V7 are scarce. Novel biomarkers that can be repetitively assessed via non-invasive methods may provide important insights into disease biology and therapeutic selection. Cell free DNA (cfDNA) is found in the blood of advanced cancer patients and potentially reflects tumor-related genetic alterations. Herein, we evaluated plasma cfDNA genetic alterations in men with CRPC. Methods: We isolated cfDNA from the plasma of 11 men with metastatic CRPC. Following library prep, paired-end sequencing was performed using Illumina Hi-Seq 2000. A bioinformatics pipeline was used for data pre-possessing including alignment, duplicate removal, normalization and variant calling. Visualization and statistical analyses were performed with SNP & Variation Suite v8.x. Additional analyses will follow on translocations. Results: Preliminary analysis of cfDNA showed stopgain mutations in CDC27, FAM104B and non-synonymous mutations in HNRNPCP5, PDE4DIP, JTB and OR2B11. Additionally, insertions were annotated in CYP1B1, CD81, and HSP90AA1 along with CD24 deletion. These genetic alterations are not yet validated using PCR or direct tumor based nucleic acid assays. Missense mutations in HNRNPCP5, PDE4DIP and OR2B11 and a deletion in CD24 have been previously reported in the genetics literature when directly sequencing tumor DNA. Conclusions: When compared to published databases, these preliminary analyses suggest but do not prove that prostate cancer specific genetic changes are detectable in plasma cfDNA. Further characterization of these alterations, in larger matched germline/tumor/plasma samples may provide insights into tumor evolution in CRPC patients. We hypothesize that these genetic changes may contain important predictive and/or prognostic information.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2015.33.7_suppl.244
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2015
detail.hit.zdb_id:
2005181-5
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