A pilot study of ultra-deep targeted sequencing of plasma DNA identifies driver mutations in hepatocellular carcinoma.

Details

Serval ID
serval:BIB_6E234F01C50C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A pilot study of ultra-deep targeted sequencing of plasma DNA identifies driver mutations in hepatocellular carcinoma.
Journal
Oncogene
Author(s)
Labgaa I., Villacorta-Martin C., D'Avola D., Craig A.J., von Felden J., Martins-Filho S.N., Sia D., Stueck A., Ward S.C., Fiel M.I., Mahajan M., Tabrizian P., Thung S.N., Ang C., Friedman S.L., Llovet J.M., Schwartz M., Villanueva A.
ISSN
1476-5594 (Electronic)
ISSN-L
0950-9232
Publication state
Published
Issued date
07/2018
Peer-reviewed
Oui
Volume
37
Number
27
Pages
3740-3752
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
Publication Status: ppublish
Abstract
Cellular components of solid tumors including DNA are released into the bloodstream, but data on circulating-free DNA (cfDNA) in hepatocellular carcinoma (HCC) are still scarce. This study aimed at analyzing mutations in cfDNA and their correlation with tissue mutations in patients with HCC. We included 8 HCC patients treated with surgical resection for whom we collected paired tissue and plasma/serum samples. We analyzed 45 specimens, including multiregional tumor tissue sampling (n = 24), peripheral blood mononuclear cells (PMBC, n = 8), plasma (n = 8) and serum (n = 5). Ultra-deep sequencing (5500× coverage) of all exons was performed in a targeted panel of 58 genes, including frequent HCC driver genes and druggable mutations. Mutations detected in plasma included known HCC oncogenes and tumor suppressors (e.g., TERT promoter, TP53, and NTRK3) as well as a candidate druggable mutation (JAK1). This approach increased the detection rates previously reported for mutations in plasma of HCC patients. A thorough characterization of cis mutations found in plasma confirmed their tumoral origin, which provides definitive evidence of the release of HCC-derived DNA fragments into the bloodstream. This study demonstrates that ultra-deep sequencing of cfDNA is feasible and can confidently detect somatic mutations found in tissue; these data reinforce the role of plasma DNA as a promising minimally invasive tool to interrogate HCC genetics.
Keywords
Adult, Aged, Carcinoma, Hepatocellular/genetics, Carcinoma, Hepatocellular/pathology, Circulating Tumor DNA/blood, Circulating Tumor DNA/genetics, DNA Mutational Analysis/methods, Discoidin Domain Receptor 2/genetics, High-Throughput Nucleotide Sequencing/methods, Humans, Janus Kinase 1/genetics, Liver Neoplasms/genetics, Liver Neoplasms/pathology, Male, Middle Aged, Mutation/genetics, Pilot Projects, Telomerase/genetics, Tumor Suppressor Protein p53/genetics
Pubmed
Web of science
Create date
14/04/2018 10:39
Last modification date
20/08/2019 15:27
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