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@ARTICLE{Mhrmann:181329,
author = {L. Möhrmann$^*$ and H. J. Huang and D. S. Hong and A. M.
Tsimberidou and S. Fu and S. A. Piha-Paul and V. Subbiah and
D. D. Karp and A. Naing and A. Krug and D. Enderle and T.
Priewasser and M. Noerholm and E. Eitan and C. Coticchia and
G. Stoll and L.-M. Jordan and C. Eng and E. S. Kopetz and J.
Skog and F. Meric-Bernstam and F. Janku},
title = {{L}iquid {B}iopsies {U}sing {P}lasma {E}xosomal {N}ucleic
{A}cids and {P}lasma {C}ell-{F}ree {DNA} {C}ompared with
{C}linical {O}utcomes of {P}atients with {A}dvanced
{C}ancers.},
journal = {Clinical cancer research},
volume = {24},
number = {1},
issn = {1078-0432},
address = {Philadelphia, Pa. [u.a.]},
publisher = {AACR},
reportid = {DKFZ-2022-01956},
pages = {181 - 188},
year = {2018},
note = {POF Topic: 317},
abstract = {Purpose: Blood-based liquid biopsies offer easy access to
genomic material for molecular diagnostics in cancer.
Commonly used cell-free DNA (cfDNA) originates from dying
cells. Exosomal nucleic acids (exoNAs) originate from living
cells, which can better reflect underlying cancer
biology.Experimental Design: Next-generation sequencing
(NGS) was used to test exoNA, and droplet digital PCR
(ddPCR) and BEAMing PCR were used to test cfDNA for
BRAFV600, KRASG12/G13, and EGFRexon19del/L858R mutations in
43 patients with progressing advanced cancers. Results were
compared with clinical testing of archival tumor tissue and
clinical outcomes.Results: Forty-one patients had BRAF,
KRAS, or EGFR mutations in tumor tissue. These mutations
were detected by NGS in $95\%$ of plasma exoNA samples, by
ddPCR in $92\%$ of cfDNA samples, and by BEAMing in $97\%$
cfDNA samples. NGS of exoNA did not detect any mutations not
present in tumor, whereas ddPCR and BEAMing detected one and
two such mutations, respectively. Compared with patients
with high exoNA mutation allelic frequency (MAF), patients
with low MAF had longer median survival (11.8 vs. 5.9
months; P = 0.006) and time to treatment failure (7.4 vs.
2.3 months; P = 0.009). A low amount of exoNA was associated
with partial response and stable disease ≥6 months (P =
0.006).Conclusions: NGS of plasma exoNA for common BRAF,
KRAS, and EGFR mutations has high sensitivity compared with
clinical testing of archival tumor and testing of plasma
cfDNA. Low exoNA MAF is an independent prognostic factor for
longer survival. Clin Cancer Res; 24(1); 181-8. ©2017
AACR.},
keywords = {Adult / Aged / Biomarkers, Tumor / Cell-Free Nucleic Acids
/ ErbB Receptors: blood / ErbB Receptors: genetics /
Exosomes / Female / Genetic Testing / Humans / Liquid
Biopsy: methods / Male / Middle Aged / Mutation / Neoplasm
Grading / Neoplasm Staging / Neoplasms: blood / Neoplasms:
diagnosis / Neoplasms: mortality / Patient Outcome
Assessment / Proto-Oncogene Proteins B-raf: blood /
Proto-Oncogene Proteins B-raf: genetics / Proto-Oncogene
Proteins p21(ras): blood / Proto-Oncogene Proteins p21(ras):
genetics / Survival Analysis / Biomarkers, Tumor (NLM
Chemicals) / Cell-Free Nucleic Acids (NLM Chemicals) / KRAS
protein, human (NLM Chemicals) / EGFR protein, human (NLM
Chemicals) / ErbB Receptors (NLM Chemicals) / BRAF protein,
human (NLM Chemicals) / Proto-Oncogene Proteins B-raf (NLM
Chemicals) / Proto-Oncogene Proteins p21(ras) (NLM
Chemicals)},
cin = {G100},
ddc = {610},
cid = {I:(DE-He78)G100-20160331},
pnm = {317 - Translational cancer research (POF3-317)},
pid = {G:(DE-HGF)POF3-317},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:29051321},
pmc = {pmc:PMC5754253},
doi = {10.1158/1078-0432.CCR-17-2007},
url = {https://inrepo02.dkfz.de/record/181329},
}