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

Seung Tae Kim,Jeeyun Lee,Young Suk Park,Ho Yeong Lim,Kee‑Taek Jang,Sujin Lee,Wooil Kwon,Joon Oh Park,Mao Mao,Shibing Deng,Jin Seok Heo,Maruja Lira,Won Ki Kang

doi:10.18632/oncotarget.5432

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.

Highlights

Biliary tract carcinomas (BTCs) are a group of tumours arising from the epithelial cells of intra- and extra-hepatic biliary ducts and gallbladder
They can be divided into gallbladder carcinoma (GBC) and cholangiocarcinoma (CC)
Thirty-eight recurrent or metastatic BTC patients were enrolled in this analysis

Summary

Introduction

Biliary tract carcinomas (BTCs) are a group of tumours arising from the epithelial cells of intra- and extra-hepatic biliary ducts and gallbladder. They can be divided into gallbladder carcinoma (GBC) and cholangiocarcinoma (CC). BTC is a rare disease with poor prognosis. Its incidence is increasing, accounting for 3% of all gastrointestinal tumours [1], but regional differences are well described [2, 3]. 10% of patients present with early stage disease and are considered candidates for curative resection. The prognosis is poor for the majority of patients with metastatic or inoperable BTC with median survival of less than 1 year [4]

Methods

Results

Conclusion