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Limits and potential of targeted sequencing analysis of liquid biopsy in patients
with lung and colon carcinoma
#MMPMID27448974
Rachiglio AM
; Esposito Abate R
; Sacco A
; Pasquale R
; Fenizia F
; Lambiase M
; Morabito A
; Montanino A
; Rocco G
; Romano C
; Nappi A
; Iaffaioli RV
; Tatangelo F
; Botti G
; Ciardiello F
; Maiello MR
; De Luca A
; Normanno N
Oncotarget
2016[Oct]; 7
(41
): 66595-66605
PMID27448974
show ga
The circulating free tumor DNA (ctDNA) represents an alternative, minimally
invasive source of tumor DNA for molecular profiling. Targeted sequencing with
next generation sequencing (NGS) can assess hundred mutations starting from a low
DNA input. We performed NGS analysis of ctDNA from 44 patients with metastatic
non-small-cell lung carcinoma (NSCLC) and 35 patients with metastatic colorectal
carcinoma (CRC). NGS detected EGFR mutations in 17/22 plasma samples from
EGFR-mutant NSCLC patients (sensitivity 77.3%). The concordance rate between
tissue and plasma in NSCLC was much lower for other mutations such as KRAS that,
based on the allelic frequency and the fraction of neoplastic cells, were likely
to be sub-clonal. NGS also identified EGFR mutations in plasma samples from two
patients with EGFR wild type tumor tissue. Both mutations were confirmed by
droplet digital PCR (ddPCR) in both plasma and tissue samples. In CRC, the
sensitivity of the NGS plasma analysis for RAS mutations was 100% (6/6) in
patients that had not resection of the primary tumor before blood drawing, and
46.2% (6/13) in patients with primary tumor resected before enrollment. Our study
showed that NGS is a suitable method for plasma testing. However, its clinical
sensitivity is significantly affected by the presence of the primary tumor and by
the heterogeneity of driver mutations.