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Pancreatic cancer: Circulating Tumor Cells and Primary Tumors show Heterogeneous KRAS Mutations

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease. Circulating tumor cells (CTC) in the blood are hypothesized as the means of systemic tumor spread. Blood obtained from healthy donors and patients with PDAC was therefore subject to size-based CTC-isolation. We additionally compared K...

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Autores principales: Kulemann, Birte, Rösch, Stephanie, Seifert, Sindy, Timme, Sylvia, Bronsert, Peter, Seifert, Gabriel, Martini, Verena, Kuvendjiska, Jasmina, Glatz, Torben, Hussung, Saskia, Fritsch, Ralph, Becker, Heiko, Pitman, Martha B., Hoeppner, Jens
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5495768/
https://www.ncbi.nlm.nih.gov/pubmed/28674438
http://dx.doi.org/10.1038/s41598-017-04601-z
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author Kulemann, Birte
Rösch, Stephanie
Seifert, Sindy
Timme, Sylvia
Bronsert, Peter
Seifert, Gabriel
Martini, Verena
Kuvendjiska, Jasmina
Glatz, Torben
Hussung, Saskia
Fritsch, Ralph
Becker, Heiko
Pitman, Martha B.
Hoeppner, Jens
author_facet Kulemann, Birte
Rösch, Stephanie
Seifert, Sindy
Timme, Sylvia
Bronsert, Peter
Seifert, Gabriel
Martini, Verena
Kuvendjiska, Jasmina
Glatz, Torben
Hussung, Saskia
Fritsch, Ralph
Becker, Heiko
Pitman, Martha B.
Hoeppner, Jens
author_sort Kulemann, Birte
collection PubMed
description Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease. Circulating tumor cells (CTC) in the blood are hypothesized as the means of systemic tumor spread. Blood obtained from healthy donors and patients with PDAC was therefore subject to size-based CTC-isolation. We additionally compared Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in pancreatic CTC and corresponding tumors, and evaluated their significance as prognostic markers. Samples from 68 individuals (58 PDAC patients, 10 healthy donors) were analyzed; CTCs were present in patients with UICC stage IA-IV tumors and none of the controls (p < 0.001). Patients with >3 CTC/ml had a trend for worse median overall survival (OS) than patients with 0.3–3 CTC/ml (P = 0.12). Surprisingly, CTCs harbored various KRAS mutations in codon 12 and 13. Patients with a KRAS (G12V) mutation in their CTC (n = 14) had a trend to better median OS (24.5 months) compared to patients with other (10 months), or no detectable KRAS mutations (8 months; P = 0.04). KRAS mutations in CTC and corresponding tumor were discordant in 11 of 26 “tumor-CTC-pairs” (42%), while 15 (58%) had a matching mutation; survival was similar in both groups (P = 0.36). Genetic characterization, including mutations such as KRAS, may prove useful for prognosis and understanding of tumor biology.
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spelling pubmed-54957682017-07-07 Pancreatic cancer: Circulating Tumor Cells and Primary Tumors show Heterogeneous KRAS Mutations Kulemann, Birte Rösch, Stephanie Seifert, Sindy Timme, Sylvia Bronsert, Peter Seifert, Gabriel Martini, Verena Kuvendjiska, Jasmina Glatz, Torben Hussung, Saskia Fritsch, Ralph Becker, Heiko Pitman, Martha B. Hoeppner, Jens Sci Rep Article Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease. Circulating tumor cells (CTC) in the blood are hypothesized as the means of systemic tumor spread. Blood obtained from healthy donors and patients with PDAC was therefore subject to size-based CTC-isolation. We additionally compared Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in pancreatic CTC and corresponding tumors, and evaluated their significance as prognostic markers. Samples from 68 individuals (58 PDAC patients, 10 healthy donors) were analyzed; CTCs were present in patients with UICC stage IA-IV tumors and none of the controls (p < 0.001). Patients with >3 CTC/ml had a trend for worse median overall survival (OS) than patients with 0.3–3 CTC/ml (P = 0.12). Surprisingly, CTCs harbored various KRAS mutations in codon 12 and 13. Patients with a KRAS (G12V) mutation in their CTC (n = 14) had a trend to better median OS (24.5 months) compared to patients with other (10 months), or no detectable KRAS mutations (8 months; P = 0.04). KRAS mutations in CTC and corresponding tumor were discordant in 11 of 26 “tumor-CTC-pairs” (42%), while 15 (58%) had a matching mutation; survival was similar in both groups (P = 0.36). Genetic characterization, including mutations such as KRAS, may prove useful for prognosis and understanding of tumor biology. Nature Publishing Group UK 2017-07-03 /pmc/articles/PMC5495768/ /pubmed/28674438 http://dx.doi.org/10.1038/s41598-017-04601-z Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Kulemann, Birte
Rösch, Stephanie
Seifert, Sindy
Timme, Sylvia
Bronsert, Peter
Seifert, Gabriel
Martini, Verena
Kuvendjiska, Jasmina
Glatz, Torben
Hussung, Saskia
Fritsch, Ralph
Becker, Heiko
Pitman, Martha B.
Hoeppner, Jens
Pancreatic cancer: Circulating Tumor Cells and Primary Tumors show Heterogeneous KRAS Mutations
title Pancreatic cancer: Circulating Tumor Cells and Primary Tumors show Heterogeneous KRAS Mutations
title_full Pancreatic cancer: Circulating Tumor Cells and Primary Tumors show Heterogeneous KRAS Mutations
title_fullStr Pancreatic cancer: Circulating Tumor Cells and Primary Tumors show Heterogeneous KRAS Mutations
title_full_unstemmed Pancreatic cancer: Circulating Tumor Cells and Primary Tumors show Heterogeneous KRAS Mutations
title_short Pancreatic cancer: Circulating Tumor Cells and Primary Tumors show Heterogeneous KRAS Mutations
title_sort pancreatic cancer: circulating tumor cells and primary tumors show heterogeneous kras mutations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5495768/
https://www.ncbi.nlm.nih.gov/pubmed/28674438
http://dx.doi.org/10.1038/s41598-017-04601-z
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