PIK3CA mutation detection in metastatic biliary cancer using cell-free DNA

Abstract

// Seung Tae Kim 1, * , Maruja Lira 2, * , Shibing Deng 2 , Sujin Lee 1 , Young Suk Park 1 , Ho Yeong Lim 1 , Won Ki Kang 1 , Mao Mao 3 , Jin Seok Heo 4 , Wooil Kwon 4 , Kee‑Taek Jang 5 , Jeeyun Lee 1, 6 , Joon Oh Park 1, 6 1 Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 2 Precision Medicine, Oncology Research Unit, Pfizer, Inc, San Diego, CA, USA 3 WuXi AppTec, Shanghai, China 4 Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 5 Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 6 Innovative Cancer Medicine Institute, Samsung Medical Center, Seoul, Korea * These authors have contributed equally to this work Correspondence to: Joon Oh Park, e-mail: oncopark@skku.edu Jeeyun Lee, e-mail: jyunlee@skku.edu Keywords: cell free DNA (cfDNA), PIK3CA mutation, droplet digital PCR (ddPCR) Received: July 13, 2015      Accepted: October 05, 2015      Published: October 16, 2015 ABSTRACT PIK3CA mutation is considered a good candidate for targeted therapies in cancers, especially biliary tract cancer (BTC). We evaluated the utility of cell free DNA (cfDNA) from serum by using droplet digital PCR (ddPCR) as an alternative source for PIK3CA mutation analysis. To identify matching archival tumour specimens from serum samples of advanced BTC patients, mutation detection using ddPCR with Bio-Rad’s PrimePCR mutation and wild type assays were performed for PIK3CA p.E542K, p.E545K, and p.H1047R. Thirty-eight patients with metastatic BTC were enrolled. Only one (BTC 29T) sample ( n = 38) was positive for PIK3CA p.E542K and another (BTC 27T) for p.H1047R mutation; none was positive for PIK3CA p.E545K. Matched serum sample (BTC 29P) was positive for PIK3CA p.E542K with 28 mutant copies detected, corresponding to 48 copies/ml of serum and an allelic prevalence of 0.3%. Another matched serum sample (BTC 27P) was positive for PIK3CA p.H1047R with 10 mutant copies detected, i.e. 18 copies/ml and an allelic frequency of 0.2%. High correlation was noted in the PIK3CA mutation status between tumour gDNA and serum cfDNA. Low-level PIK3CA mutations were detectable in the serum indicating the utility of cfDNA as a DNA source to detect cancer-derived mutations in metastatic biliary cancers.