Detection of mutations in circulating cell‐free DNA in relation to disease stage in colorectal cancer
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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2019-07-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.2219 |
| _version_ | 1819084003476504576 |
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| author | Sandra Liebs Ulrich Keilholz Inge Kehler Caroline Schweiger Johannes Haybäck Anika Nonnenmacher |
| author_facet | Sandra Liebs Ulrich Keilholz Inge Kehler Caroline Schweiger Johannes Haybäck Anika Nonnenmacher |
| author_sort | Sandra Liebs |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T20:41:33Z |
| format | Article |
| id | doaj.art-8a815133ce8d40bbb17a03416f996661 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-12-21T20:41:33Z |
| publishDate | 2019-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-8a815133ce8d40bbb17a03416f9966612022-12-21T18:50:57ZengWileyCancer Medicine2045-76342019-07-01883761376910.1002/cam4.2219Detection of mutations in circulating cell‐free DNA in relation to disease stage in colorectal cancerSandra Liebs0Ulrich Keilholz1Inge Kehler2Caroline Schweiger3Johannes Haybäck4Anika Nonnenmacher5German Cancer Consortium (DKTK) German Cancer Research Center (DKFZ) Heidelberg GermanyCharité ‐ Universitätsmedizin Berlin, corporate member of Freie Universität BerlinHumboldt-Universität zu Berlin, and Berlin Institute of HealthCharité Comprehensive Cancer CenterBerlin GermanyCharité ‐ Universitätsmedizin Berlin, corporate member of Freie Universität BerlinHumboldt-Universität zu Berlin, and Berlin Institute of HealthCharité Comprehensive Cancer CenterBerlin GermanyInstitute of Pathology, Medical University Graz Graz AustriaInstitute of Pathology, Medical University Graz Graz AustriaCharité ‐ Universitätsmedizin Berlin, corporate member of Freie Universität BerlinHumboldt-Universität zu Berlin, and Berlin Institute of HealthCharité Comprehensive Cancer CenterBerlin GermanyAbstract 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.https://doi.org/10.1002/cam4.2219BRAFcirculating cell‐free DNAcolorectal cancerKRAS |
| spellingShingle | Sandra Liebs Ulrich Keilholz Inge Kehler Caroline Schweiger Johannes Haybäck Anika Nonnenmacher Detection of mutations in circulating cell‐free DNA in relation to disease stage in colorectal cancer Cancer Medicine BRAF circulating cell‐free DNA colorectal cancer KRAS |
| title | Detection of mutations in circulating cell‐free DNA in relation to disease stage in colorectal cancer |
| title_full | Detection of mutations in circulating cell‐free DNA in relation to disease stage in colorectal cancer |
| title_fullStr | Detection of mutations in circulating cell‐free DNA in relation to disease stage in colorectal cancer |
| title_full_unstemmed | Detection of mutations in circulating cell‐free DNA in relation to disease stage in colorectal cancer |
| title_short | Detection of mutations in circulating cell‐free DNA in relation to disease stage in colorectal cancer |
| title_sort | detection of mutations in circulating cell free dna in relation to disease stage in colorectal cancer |
| topic | BRAF circulating cell‐free DNA colorectal cancer KRAS |
| url | https://doi.org/10.1002/cam4.2219 |
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