Pancreatic cancer: Circulating Tumor Cells and Primary Tumors show Heterogeneous KRAS Mutations
Abstract 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 c...
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Nature Portfolio
2017
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oai:doaj.org-article:3c8818e189834f428dc9c5e17abf9a172021-12-02T11:40:34ZPancreatic cancer: Circulating Tumor Cells and Primary Tumors show Heterogeneous KRAS Mutations10.1038/s41598-017-04601-z2045-2322https://doaj.org/article/3c8818e189834f428dc9c5e17abf9a172017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04601-zhttps://doaj.org/toc/2045-2322Abstract 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.Birte KulemannStephanie RöschSindy SeifertSylvia TimmePeter BronsertGabriel SeifertVerena MartiniJasmina KuvendjiskaTorben GlatzSaskia HussungRalph FritschHeiko BeckerMartha B. PitmanJens HoeppnerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017) |
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Medicine R Science Q |
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Medicine R Science Q Birte Kulemann Stephanie Rösch Sindy Seifert Sylvia Timme Peter Bronsert Gabriel Seifert Verena Martini Jasmina Kuvendjiska Torben Glatz Saskia Hussung Ralph Fritsch Heiko Becker Martha B. Pitman Jens Hoeppner Pancreatic cancer: Circulating Tumor Cells and Primary Tumors show Heterogeneous KRAS Mutations |
| description |
Abstract 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. |
| format |
article |
| author |
Birte Kulemann Stephanie Rösch Sindy Seifert Sylvia Timme Peter Bronsert Gabriel Seifert Verena Martini Jasmina Kuvendjiska Torben Glatz Saskia Hussung Ralph Fritsch Heiko Becker Martha B. Pitman Jens Hoeppner |
| author_facet |
Birte Kulemann Stephanie Rösch Sindy Seifert Sylvia Timme Peter Bronsert Gabriel Seifert Verena Martini Jasmina Kuvendjiska Torben Glatz Saskia Hussung Ralph Fritsch Heiko Becker Martha B. Pitman Jens Hoeppner |
| author_sort |
Birte Kulemann |
| title |
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_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_sort |
pancreatic cancer: circulating tumor cells and primary tumors show heterogeneous kras mutations |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/3c8818e189834f428dc9c5e17abf9a17 |
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