Sequencing of RAS/RAF pathway genes in primary colorectal cancer and matched liver and lung metastases
| Autor: | Nikki Knijn, Sietske Riemersma, Cornelis J. A. Punt, Leonie J. M. Mekenkamp, Iris D. Nagtegaal, Carlijn van de Water, Jos Meijer, Maria Tebar, Shannon van Vliet, Femke Simmer |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Neuroblastoma RAS viral oncogene homolog Colorectal cancer medicine.medical_treatment Concordance Molecular Inversion Probe medicine.disease_cause lcsh:RC254-282 DNA sequencing Targeted therapy 03 medical and health sciences Liver metastases 0302 clinical medicine Next generation sequencing Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14] Medicine HRAS Molecular Biology neoplasms business.industry General Medicine medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens 030104 developmental biology 030220 oncology & carcinogenesis Cancer research KRAS business Lung metastases |
| Zdroj: | Applied Cancer Research, Vol 39, Iss 1, Pp 1-7 (2019) Applied Cancer Research, 39, pp. 9 Applied Cancer Research, 39, 9 |
| ISSN: | 1980-5578 1808-5512 |
| DOI: | 10.1186/s41241-019-0079-y |
| Popis: | Background Mutations in the RAS/RAF pathway predict resistance to anti-epidermal growth factor receptor antibodies in colorectal cancer (CRC), and may be targets for future therapies. This study investigates concordance of BRAF, HRAS, KRAS, NRAS and PIK3CA mutation status in primary CRC with matched liver (n = 274), lung (n = 114) or combined liver and lung metastases (n = 14). Methods Next generation sequencing was performed on DNA from formalin-fixed paraffin embedded CRC and matched liver and/or lung metastases, for recurrent mutations in BRAF, HRAS, KRAS, NRAS and PIK3CA and using the single-molecule molecular inversion probe method. Results Paired sequencing results on all five genes were reached in 249 of the 402 cases (62%). The obtained number of unique reads was not always sufficient to confidently call the absence or presence of mutations for all regions of interest. The mutational status of matched pairs was highly concordant; 91.1% concordance for all five genes, 95.5% for KRAS, 99.1% for NRAS. Lung metastases more often harboured RAS mutations compared to liver metastases (71% vs. 48%, p Conclusions In this large series of CRC we show that both primary tumors and corresponding metastases can be used to determine the mutational status for targeted therapy, given the high concordance rates. Next generation sequencing including a single molecule tags is feasible, however in combination with archival formalin-fixed paraffin embedded material is limited by coverage depth. |
| Databáze: | OpenAIRE |
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