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5 results on '"Kehler, Inge"'

2. Detection of mutations in circulating cell‐free DNA in relation to disease stage in colorectal cancer

Author

Liebs, Sandra, Keilholz, Ulrich, Kehler, Inge, Schweiger, Caroline, Hayb��ck, Johannes, and Nonnenmacher, Anika

Subjects
Adult, Male, Proto-Oncogene Proteins B-raf, DNA Mutational Analysis, colorectal cancer, lcsh:RC254-282, Circulating Tumor DNA, BRAF, Proto-Oncogene Proteins p21(ras), Biomarkers, Tumor, KRAS, Humans, Early Detection of Cancer, Aged, Original Research, Aged, 80 and over, circulating cell‐free DNA, Liquid Biopsy, Clinical Cancer Research, DNA, Neoplasm, Middle Aged, circulating cell-free DNA, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, digestive system diseases, Mutation, Female, Colorectal Neoplasms, Cell-Free Nucleic Acids, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
Abstract

Enthusiasm has emerged for the potential of liquid biopsies to provide easily accessible genetic biomarkers for early diagnosis and mutational cancer characterization. We here systematically investigated the suitability of circulating cell‐free DNA (cfDNA) analysis for mutation detection in colorectal cancer (CRC) patients with respect to clinicopathological disease stage. Droplet Digital PCR (ddPCR) was performed to detect common point mutations in the KRAS and BRAF oncogenes in cfDNA from 65 patients and compared to mutations in tumor tissue. Stage of disease was classified according to UICC (Union for International Cancer Control) criteria. In tumor tissue, KRAS or BRAF mutations were present in 35 of 65 cases (44% UICC stage I, 50% stage II, 47% stage III, and 62% stage IV). Although cfDNA was detected in 100% of patients, ddPCR displayed the tumor tissue mutation in only 1 of 6 (17%) stage II patients, whereas 10 of 18 (56%) reported variants were verified in cfDNA samples of the stage IV cohort. No BRAF or KRAS mutation was detected in cfDNA from patients with wild‐type tumor tissue. In one case of mutant stage II colon cancer (KRAS‐G12C), the G12D variant was detected in cfDNA instead. Further workup revealed that circulating tumor‐derived DNA and liver metastases originated from a synchronous KRAS‐mutated cancer of the pancreas. Our results demonstrate that ddPCR‐based analysis is highly specific and useful for mutation monitoring, but the sensitivity limits its usefulness for early cancer detection.

Published
2019

4. Molecular dissection of colorectal cancer in pre-clinical models identifies biomarkers predicting sensitivity to EGFR inhibitors

Author

Schuette, Moritz, Risch, Thomas, Abdavi-Azar, Nilofar, Boehnke, Karsten, Schumacher, Dirk, Keil, Marlen, Yildirimman, Reha, Jandrasits, Christine, Borodina, Tatiana, Amstislavskiy, Vyacheslav, Worth, Catherine L., Schweiger, Caroline, Liebs, Sandra, Lange, Martin, Warnatz, Hans-Joerg, Butcher, Lee M., Barrett, James E., Sultan, Marc, Wierling, Christoph, Golob-Schwarzl, Nicole, Lax, Sigurd, Uranitsch, Stefan, Becker, Michael, Welte, Yvonne, Regan, Joseph Lewis, Silvestrov, Maxine, Kehler, Inge, Fusi, Alberto, Kessler, Thomas, Herwig, Ralf, Landegren, Ulf, Wienke, Dirk, Nilsson, Mats, Velasco, Juan A., Garin-Chesa, Pilar, Reinhard, Christoph, Beck, Stephan, Schaefer, Reinhold, Regenbrecht, Christian R. A., Henderson, David, Lange, Bodo, Haybaeck, Johannes, Keilholz, Ulrich, Hoffmann, Jens, Lehrach, Hans, Yaspo, Marie-Laure, Schuette, Moritz, Risch, Thomas, Abdavi-Azar, Nilofar, Boehnke, Karsten, Schumacher, Dirk, Keil, Marlen, Yildirimman, Reha, Jandrasits, Christine, Borodina, Tatiana, Amstislavskiy, Vyacheslav, Worth, Catherine L., Schweiger, Caroline, Liebs, Sandra, Lange, Martin, Warnatz, Hans-Joerg, Butcher, Lee M., Barrett, James E., Sultan, Marc, Wierling, Christoph, Golob-Schwarzl, Nicole, Lax, Sigurd, Uranitsch, Stefan, Becker, Michael, Welte, Yvonne, Regan, Joseph Lewis, Silvestrov, Maxine, Kehler, Inge, Fusi, Alberto, Kessler, Thomas, Herwig, Ralf, Landegren, Ulf, Wienke, Dirk, Nilsson, Mats, Velasco, Juan A., Garin-Chesa, Pilar, Reinhard, Christoph, Beck, Stephan, Schaefer, Reinhold, Regenbrecht, Christian R. A., Henderson, David, Lange, Bodo, Haybaeck, Johannes, Keilholz, Ulrich, Hoffmann, Jens, Lehrach, Hans, and Yaspo, Marie-Laure

Abstract

Colorectal carcinoma represents a heterogeneous entity, with only a fraction of the tumours responding to available therapies, requiring a better molecular understanding of the disease in precision oncology. To address this challenge, the OncoTrack consortium recruited 106 CRC patients (stages I-IV) and developed a pre-clinical platform generating a compendium of drug sensitivity data totalling 44,000 assays testing 16 clinical drugs on patient-derived in vivo and in vitro models. This large biobank of 106 tumours, 35 organoids and 59 xenografts, with extensive omics data comparing donor tumours and derived models provides a resource for advancing our understanding of CRC. Models recapitulate many of the genetic and transcriptomic features of the donors, but defined less complex molecular sub-groups because of the loss of human stroma. Linking molecular profiles with drug sensitivity patterns identifies novel biomarkers, including a signature outperforming RAS/RAF mutations in predicting sensitivity to the EGFR inhibitor cetuximab.

Published
2017
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5. Molecular dissection of colorectal cancer in pre-clinical models identifies biomarkers predicting sensitivity to EGFR inhibitors

Author

Schütte, Moritz, primary, Risch, Thomas, additional, Abdavi-Azar, Nilofar, additional, Boehnke, Karsten, additional, Schumacher, Dirk, additional, Keil, Marlen, additional, Yildiriman, Reha, additional, Jandrasits, Christine, additional, Borodina, Tatiana, additional, Amstislavskiy, Vyacheslav, additional, Worth, Catherine L., additional, Schweiger, Caroline, additional, Liebs, Sandra, additional, Lange, Martin, additional, Warnatz, Hans- Jörg, additional, Butcher, Lee M., additional, Barrett, James E., additional, Sultan, Marc, additional, Wierling, Christoph, additional, Golob-Schwarzl, Nicole, additional, Lax, Sigurd, additional, Uranitsch, Stefan, additional, Becker, Michael, additional, Welte, Yvonne, additional, Regan, Joseph Lewis, additional, Silvestrov, Maxine, additional, Kehler, Inge, additional, Fusi, Alberto, additional, Kessler, Thomas, additional, Herwig, Ralf, additional, Landegren, Ulf, additional, Wienke, Dirk, additional, Nilsson, Mats, additional, Velasco, Juan A., additional, Garin-Chesa, Pilar, additional, Reinhard, Christoph, additional, Beck, Stephan, additional, Schäfer, Reinhold, additional, Regenbrecht, Christian R. A., additional, Henderson, David, additional, Lange, Bodo, additional, Haybaeck, Johannes, additional, Keilholz, Ulrich, additional, Hoffmann, Jens, additional, Lehrach, Hans, additional, and Yaspo, Marie-Laure, additional

Published
2017
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