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...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2017-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-04601-z |
| _version_ | 1818857711820865536 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T08:44:44Z |
| format | Article |
| id | doaj.art-3c8818e189834f428dc9c5e17abf9a17 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-19T08:44:44Z |
| publishDate | 2017-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-3c8818e189834f428dc9c5e17abf9a172022-12-21T20:28:49ZengNature PortfolioScientific Reports2045-23222017-07-017111110.1038/s41598-017-04601-zPancreatic cancer: Circulating Tumor Cells and Primary Tumors show Heterogeneous KRAS MutationsBirte Kulemann0Stephanie Rösch1Sindy Seifert2Sylvia Timme3Peter Bronsert4Gabriel Seifert5Verena Martini6Jasmina Kuvendjiska7Torben Glatz8Saskia Hussung9Ralph Fritsch10Heiko Becker11Martha B. Pitman12Jens Hoeppner13Center for Surgery, Department of General and Visceral Surgery, Medical Center University of FreiburgCenter for Surgery, Department of General and Visceral Surgery, Medical Center University of FreiburgCenter for Surgery, Department of General and Visceral Surgery, Medical Center University of FreiburgInstitute for Surgical Pathology, Medical Center University of FreiburgInstitute for Surgical Pathology, Medical Center University of FreiburgCenter for Surgery, Department of General and Visceral Surgery, Medical Center University of FreiburgCenter for Surgery, Department of General and Visceral Surgery, Medical Center University of FreiburgCenter for Surgery, Department of General and Visceral Surgery, Medical Center University of FreiburgCenter for Surgery, Department of General and Visceral Surgery, Medical Center University of FreiburgCenter of Medicine, Department of Medicine I, Medical Center University of FreiburgCenter of Medicine, Department of Medicine I, Medical Center University of FreiburgCenter of Medicine, Department of Medicine I, Medical Center University of FreiburgDepartment of Pathology & Andrew L. Warshaw, MD Institute for Pancreatic Cancer Research, Massachusetts General Hospital/Harvard Medical SchoolCenter for Surgery, Department of General and Visceral Surgery, Medical Center University of FreiburgAbstract 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.https://doi.org/10.1038/s41598-017-04601-z |
| spellingShingle | 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 Scientific Reports |
| 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 |
| url | https://doi.org/10.1038/s41598-017-04601-z |
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