PortalPublikationenA pilot study of ultra-deep targeted sequencing of plasma DN...

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

Standard

A pilot study of ultra-deep targeted sequencing of plasma DNA identifies driver mutations in hepatocellular carcinoma. / Labgaa, Ismail; Villacorta-Martin, Carlos; D'Avola, Delia; Craig, Amanda J; von Felden, Johann; Martins-Filho, Sebastiao N; Sia, Daniela; Stueck, Ashley; Ward, Stephen C; Fiel, M Isabel; Mahajan, Milind; Tabrizian, Parissa; Thung, Swan N; Ang, Celina; Friedman, Scott L; Llovet, Josep M; Schwartz, Myron; Villanueva, Augusto.

in: ONCOGENE, Jahrgang 37, Nr. 27, 07.2018, S. 3740-3752.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Labgaa, I, Villacorta-Martin, C, D'Avola, D, Craig, AJ, von Felden, J, Martins-Filho, SN, Sia, D, Stueck, A, Ward, SC, Fiel, MI, Mahajan, M, Tabrizian, P, Thung, SN, Ang, C, Friedman, SL, Llovet, JM, Schwartz, M & Villanueva, A 2018, 'A pilot study of ultra-deep targeted sequencing of plasma DNA identifies driver mutations in hepatocellular carcinoma', ONCOGENE, Jg. 37, Nr. 27, S. 3740-3752. https://doi.org/10.1038/s41388-018-0206-3

APA

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. (2018). A pilot study of ultra-deep targeted sequencing of plasma DNA identifies driver mutations in hepatocellular carcinoma. ONCOGENE, 37(27), 3740-3752. https://doi.org/10.1038/s41388-018-0206-3

Vancouver

Labgaa I, Villacorta-Martin C, D'Avola D, Craig AJ, von Felden J, Martins-Filho SN et al. A pilot study of ultra-deep targeted sequencing of plasma DNA identifies driver mutations in hepatocellular carcinoma. ONCOGENE. 2018 Jul;37(27):3740-3752. https://doi.org/10.1038/s41388-018-0206-3

Bibtex

@article{db78139ac04f4e4bb9d238826efeef17,
title = "A pilot study of ultra-deep targeted sequencing of plasma DNA identifies driver mutations in hepatocellular carcinoma",
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 = "Journal Article",
author = "Ismail Labgaa and Carlos Villacorta-Martin and Delia D'Avola and Craig, {Amanda J} and {von Felden}, Johann and Martins-Filho, {Sebastiao N} and Daniela Sia and Ashley Stueck and Ward, {Stephen C} and Fiel, {M Isabel} and Milind Mahajan and Parissa Tabrizian and Thung, {Swan N} and Celina Ang and Friedman, {Scott L} and Llovet, {Josep M} and Myron Schwartz and Augusto Villanueva",
year = "2018",
month = jul,
doi = "10.1038/s41388-018-0206-3",
language = "English",
volume = "37",
pages = "3740--3752",
journal = "ONCOGENE",
issn = "0950-9232",
publisher = "NATURE PUBLISHING GROUP",
number = "27",

}

RIS

TY - JOUR

T1 - A pilot study of ultra-deep targeted sequencing of plasma DNA identifies driver mutations in hepatocellular carcinoma

AU - Labgaa, Ismail

AU - Villacorta-Martin, Carlos

AU - D'Avola, Delia

AU - Craig, Amanda J

AU - von Felden, Johann

AU - Martins-Filho, Sebastiao N

AU - Sia, Daniela

AU - Stueck, Ashley

AU - Ward, Stephen C

AU - Fiel, M Isabel

AU - Mahajan, Milind

AU - Tabrizian, Parissa

AU - Thung, Swan N

AU - Ang, Celina

AU - Friedman, Scott L

AU - Llovet, Josep M

AU - Schwartz, Myron

AU - Villanueva, Augusto

PY - 2018/7

Y1 - 2018/7

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1038/s41388-018-0206-3

DO - 10.1038/s41388-018-0206-3

M3 - SCORING: Journal article

C2 - 29628508

VL - 37

SP - 3740

EP - 3752

JO - ONCOGENE

JF - ONCOGENE

SN - 0950-9232

IS - 27

ER -