Somatic alterations in circulating cell-free DNA of oesophageal carcinoma patients during primary staging are indicative for post-surgical tumour recurrence
Abstract Oesophageal cancer (OC) has high mortality. This study aims at determining the feasibility of liquid biopsies for genomic profiling in early stage OC, comparing two different technologies for mutational analysis in circulating cell -free DNA (ccfDNA) and evaluating the clinical impact of th...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Portfolio
2018
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/e866facbb8674b04bb198aaa07a3731b |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:e866facbb8674b04bb198aaa07a3731b |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:e866facbb8674b04bb198aaa07a3731b2021-12-02T15:08:42ZSomatic alterations in circulating cell-free DNA of oesophageal carcinoma patients during primary staging are indicative for post-surgical tumour recurrence10.1038/s41598-018-33027-42045-2322https://doaj.org/article/e866facbb8674b04bb198aaa07a3731b2018-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-33027-4https://doaj.org/toc/2045-2322Abstract Oesophageal cancer (OC) has high mortality. This study aims at determining the feasibility of liquid biopsies for genomic profiling in early stage OC, comparing two different technologies for mutational analysis in circulating cell -free DNA (ccfDNA) and evaluating the clinical impact of these somatic alterations during primary staging. In 25 patients with locally advanced OC, endoscopic tumour biopsies and simultaneous blood samples were taken during primary staging. Genomic DNA from biopsies and ccfDNA were analysed for mutations using a 12 gene panel next-generation sequencing (NGS) assay as well as digital droplet PCR (ddPCR). Genetic data was correlated with patients’ outcome. In 21 of the tested biopsies (84%) at least one somatic mutation was detected by NGS. Mutations detected by NGS were detectable by ddPCR with similar allele frequencies. In three out of the 21 patients with proven mutations, the same mutations were also detectable in ccfDNA using NGS (14%). In contrast, ddPCR detected mutations in ccfDNA of five additional patients (8/21, 38%). Post-surgical outcome analysis was performed for those patients who had received complete tumour resection (n = 16). Five of them suffered from an early relapse within the first year after surgery, including four with detectable somatic mutations in ccfDNA during primary staging. Taken together, we showed a higher sensitivity for ddPCR compared to NGS in detecting mutated ccfDNA in OC. Detection of somatically altered ccfDNA during primary staging seems to be indicative for post-surgical tumour recurrence.Helen PasternackJana FassunkePatrick Sven PlumSeung-Hun ChonDaniel Alexander HeschelerAsmae GassaSabine Merkelbach-BruseChristiane Josephine BrunsSven PernerMichael HallekReinhard BüttnerElfriede BollschweilerArnulf Heinrich HölscherAlexander QuaasThomas ZanderJonathan WeissHakan AlakusNature PortfolioarticleSomatic AlterationsPrimary StageccfDNASimultaneous Blood SamplesPost-surgical OutcomesMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-8 (2018) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Somatic Alterations Primary Stage ccfDNA Simultaneous Blood Samples Post-surgical Outcomes Medicine R Science Q |
| spellingShingle |
Somatic Alterations Primary Stage ccfDNA Simultaneous Blood Samples Post-surgical Outcomes Medicine R Science Q Helen Pasternack Jana Fassunke Patrick Sven Plum Seung-Hun Chon Daniel Alexander Hescheler Asmae Gassa Sabine Merkelbach-Bruse Christiane Josephine Bruns Sven Perner Michael Hallek Reinhard Büttner Elfriede Bollschweiler Arnulf Heinrich Hölscher Alexander Quaas Thomas Zander Jonathan Weiss Hakan Alakus Somatic alterations in circulating cell-free DNA of oesophageal carcinoma patients during primary staging are indicative for post-surgical tumour recurrence |
| description |
Abstract Oesophageal cancer (OC) has high mortality. This study aims at determining the feasibility of liquid biopsies for genomic profiling in early stage OC, comparing two different technologies for mutational analysis in circulating cell -free DNA (ccfDNA) and evaluating the clinical impact of these somatic alterations during primary staging. In 25 patients with locally advanced OC, endoscopic tumour biopsies and simultaneous blood samples were taken during primary staging. Genomic DNA from biopsies and ccfDNA were analysed for mutations using a 12 gene panel next-generation sequencing (NGS) assay as well as digital droplet PCR (ddPCR). Genetic data was correlated with patients’ outcome. In 21 of the tested biopsies (84%) at least one somatic mutation was detected by NGS. Mutations detected by NGS were detectable by ddPCR with similar allele frequencies. In three out of the 21 patients with proven mutations, the same mutations were also detectable in ccfDNA using NGS (14%). In contrast, ddPCR detected mutations in ccfDNA of five additional patients (8/21, 38%). Post-surgical outcome analysis was performed for those patients who had received complete tumour resection (n = 16). Five of them suffered from an early relapse within the first year after surgery, including four with detectable somatic mutations in ccfDNA during primary staging. Taken together, we showed a higher sensitivity for ddPCR compared to NGS in detecting mutated ccfDNA in OC. Detection of somatically altered ccfDNA during primary staging seems to be indicative for post-surgical tumour recurrence. |
| format |
article |
| author |
Helen Pasternack Jana Fassunke Patrick Sven Plum Seung-Hun Chon Daniel Alexander Hescheler Asmae Gassa Sabine Merkelbach-Bruse Christiane Josephine Bruns Sven Perner Michael Hallek Reinhard Büttner Elfriede Bollschweiler Arnulf Heinrich Hölscher Alexander Quaas Thomas Zander Jonathan Weiss Hakan Alakus |
| author_facet |
Helen Pasternack Jana Fassunke Patrick Sven Plum Seung-Hun Chon Daniel Alexander Hescheler Asmae Gassa Sabine Merkelbach-Bruse Christiane Josephine Bruns Sven Perner Michael Hallek Reinhard Büttner Elfriede Bollschweiler Arnulf Heinrich Hölscher Alexander Quaas Thomas Zander Jonathan Weiss Hakan Alakus |
| author_sort |
Helen Pasternack |
| title |
Somatic alterations in circulating cell-free DNA of oesophageal carcinoma patients during primary staging are indicative for post-surgical tumour recurrence |
| title_short |
Somatic alterations in circulating cell-free DNA of oesophageal carcinoma patients during primary staging are indicative for post-surgical tumour recurrence |
| title_full |
Somatic alterations in circulating cell-free DNA of oesophageal carcinoma patients during primary staging are indicative for post-surgical tumour recurrence |
| title_fullStr |
Somatic alterations in circulating cell-free DNA of oesophageal carcinoma patients during primary staging are indicative for post-surgical tumour recurrence |
| title_full_unstemmed |
Somatic alterations in circulating cell-free DNA of oesophageal carcinoma patients during primary staging are indicative for post-surgical tumour recurrence |
| title_sort |
somatic alterations in circulating cell-free dna of oesophageal carcinoma patients during primary staging are indicative for post-surgical tumour recurrence |
| publisher |
Nature Portfolio |
| publishDate |
2018 |
| url |
https://doaj.org/article/e866facbb8674b04bb198aaa07a3731b |
| work_keys_str_mv |
AT helenpasternack somaticalterationsincirculatingcellfreednaofoesophagealcarcinomapatientsduringprimarystagingareindicativeforpostsurgicaltumourrecurrence AT janafassunke somaticalterationsincirculatingcellfreednaofoesophagealcarcinomapatientsduringprimarystagingareindicativeforpostsurgicaltumourrecurrence AT patricksvenplum somaticalterationsincirculatingcellfreednaofoesophagealcarcinomapatientsduringprimarystagingareindicativeforpostsurgicaltumourrecurrence AT seunghunchon somaticalterationsincirculatingcellfreednaofoesophagealcarcinomapatientsduringprimarystagingareindicativeforpostsurgicaltumourrecurrence AT danielalexanderhescheler somaticalterationsincirculatingcellfreednaofoesophagealcarcinomapatientsduringprimarystagingareindicativeforpostsurgicaltumourrecurrence AT asmaegassa somaticalterationsincirculatingcellfreednaofoesophagealcarcinomapatientsduringprimarystagingareindicativeforpostsurgicaltumourrecurrence AT sabinemerkelbachbruse somaticalterationsincirculatingcellfreednaofoesophagealcarcinomapatientsduringprimarystagingareindicativeforpostsurgicaltumourrecurrence AT christianejosephinebruns somaticalterationsincirculatingcellfreednaofoesophagealcarcinomapatientsduringprimarystagingareindicativeforpostsurgicaltumourrecurrence AT svenperner somaticalterationsincirculatingcellfreednaofoesophagealcarcinomapatientsduringprimarystagingareindicativeforpostsurgicaltumourrecurrence AT michaelhallek somaticalterationsincirculatingcellfreednaofoesophagealcarcinomapatientsduringprimarystagingareindicativeforpostsurgicaltumourrecurrence AT reinhardbuttner somaticalterationsincirculatingcellfreednaofoesophagealcarcinomapatientsduringprimarystagingareindicativeforpostsurgicaltumourrecurrence AT elfriedebollschweiler somaticalterationsincirculatingcellfreednaofoesophagealcarcinomapatientsduringprimarystagingareindicativeforpostsurgicaltumourrecurrence AT arnulfheinrichholscher somaticalterationsincirculatingcellfreednaofoesophagealcarcinomapatientsduringprimarystagingareindicativeforpostsurgicaltumourrecurrence AT alexanderquaas somaticalterationsincirculatingcellfreednaofoesophagealcarcinomapatientsduringprimarystagingareindicativeforpostsurgicaltumourrecurrence AT thomaszander somaticalterationsincirculatingcellfreednaofoesophagealcarcinomapatientsduringprimarystagingareindicativeforpostsurgicaltumourrecurrence AT jonathanweiss somaticalterationsincirculatingcellfreednaofoesophagealcarcinomapatientsduringprimarystagingareindicativeforpostsurgicaltumourrecurrence AT hakanalakus somaticalterationsincirculatingcellfreednaofoesophagealcarcinomapatientsduringprimarystagingareindicativeforpostsurgicaltumourrecurrence |
| _version_ |
1718388096386465792 |