KRAS mutations in the parental tumour accelerate in vitro growth of tumoroids established from colorectal adenocarcinoma
Research output: Contribution to journal › Journal article › Research › peer-review
Documents
- KRAS mutations in the parental tumour accelerate in vitro growth of tumoroids (Acc. manuscript)
Accepted author manuscript, 524 KB, PDF document
The aim of the present study was to characterize a patient-derived in vitro 3D model (ie tumoroid) established from colorectal adenocarcinoma. This study investigated the growth rate of tumoroids and whether the Kirsten rat sarcoma (KRAS) mutations in the parental tumour accelerate this rate. The tumoroids were established from surgical resections of primary and metastatic colorectal adenocarcinoma from 26 patients. The in vitro growth rate of these tumoroids was monitored by automated imaging and recorded as relative growth rate. The KRAS hotspot mutations were investigated on the parental tumours by Ion Torrent™ next-generation sequencing. The KRAS mutations were detected in 58% of the parental tumours, and a significantly higher growth rate was observed for tumoroids established from the KRAS-mutated tumours compared to wild-type tumours (P < 0.0001). The average relative growth rate (log10) on day 10 was 0.360 ± 0.180 (mean ± SD) for the KRAS-mutated group and 0.098 ± 0.135 (mean ± SD) for the KRAS wild-type group. These results showed that the presence of KRAS mutations in parental tumours is associated with an acceleration of the growth rate of tumoroids. The future perspective for such a model could be the implementation of chemoassays for personalized medicine.
Original language | English |
---|---|
Journal | International Journal of Experimental Pathology |
Volume | 100 |
Issue number | 1 |
Pages (from-to) | 12-18 |
Number of pages | 7 |
ISSN | 0959-9673 |
DOIs | |
Publication status | Published - Feb 2019 |
- Adenocarcinoma/genetics, Aged, Aged, 80 and over, Cell Proliferation, Colorectal Neoplasms/genetics, DNA Mutational Analysis/methods, Female, Genetic Predisposition to Disease, High-Throughput Nucleotide Sequencing, Humans, Male, Middle Aged, Mutation, Organoids, Phenotype, Proto-Oncogene Proteins p21(ras)/genetics, Time Factors, Tumor Cells, Cultured
Research areas
Number of downloads are based on statistics from Google Scholar and www.ku.dk
ID: 235000152