A pilot study of ultra-deep targeted sequencing of plasma DNA identifies driver mutations in hepatocellular carcinoma
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 incl...
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Veröffentlicht in: | Oncogene 2018-07, Vol.37 (27), p.3740-3752 |
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Sprache: | eng |
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Zusammenfassung: | 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. |
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ISSN: | 0950-9232 1476-5594 |
DOI: | 10.1038/s41388-018-0206-3 |