Plasma cell-free DNA profiling of PI3K/Akt pathway aberrations in two multi-institutional independent metastatic castration-resistant prostate cancer (mCRPC) cohorts.
Edmond Michael Kwan, Chao Dai, Heidi Fettke, Christine Hauser, Patricia Bukczynska, Nicole Ng, Siavash Foroughi, Lisa-Jane K Graham, Kate Lynette Mahon, Winston Tan, Amy Wang, Zhixin Zhao, Tiantian Zheng, Kemin Zhou, Jian-Jun Yu, Peter Du, Lisa Horvath, Shidong Jia, Manish Kohli, Arun Azad
JOURNAL OF CLINICAL ONCOLOGY | LIPPINCOTT WILLIAMS & WILKINS | Published : 2021
159 Background: Tumour tissue from metastatic castration-resistant prostate cancer (mCRPC) harbors frequent copy number variations (CNVs) in the phosphatidylinositol-3-kinase (PI3K)/Akt-signaling pathway. However, identifying CNVs in plasma cell-free DNA (cfDNA) has proven challenging. With emerging data supporting Akt inhibition in PTEN-deficient mCRPC, cfDNA assays for robustly identifying PI3K/Akt pathway aberrations including CNVs are urgently required. Methods: In this multi-institutional prospective biomarker study, we used the Predicine cfDNA assay, optimised for CNV detection, to perform targeted sequencing in 231 mCRPC patients in two independent cohorts (Australian, n = 78; US, n ..View full abstract