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Anticancer Res. 2019 Nov;39(11):5867-5877. doi: 10.21873/anticanres.13791.

Clonal Evolution of MEK/MAPK Pathway Activating Mutations in a Metastatic Colorectal Cancer Case.

Author information

1
Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland kaisa.lehtomaki@tuni.fi.
2
Tays Cancer Center, Tampere University Hospital, Tampere, Finland.
3
Central Finland Central Hospital, Jyväskylä, Finland.
4
Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
5
Pathology, Fimlab Laboratories, Tampere, Finland.
6
Misvik Biology Ltd, Turku, Finland.
7
University of Sheffield, Sheffield, U.K.
8
Docrates Cancer Center, Helsinki, Finland.

Abstract

BACKGROUND/AIM:

The aim of this study was to examine clonal heterogeneity, to test the utility of liquid biopsy in monitoring disease progression and to evaluate the usefulness of ex vivo drug screening in a BRAF L597Q-mutated colorectal cancer (CRC) patient developing metastases during adjuvant therapy.

MATERIALS AND METHODS:

Next generation sequencing (NGS) and droplet digital PCR (ddPCR) were performed in samples from tumor tissues and liquid biopsies. Live cancer cells from a metastatic lesion were used in ex vivo drug sensitivity assays.

RESULTS:

We found evidence of continued dependence of MEK/MAPK pathway activation, but different activating mutations in primary tumor and metastases. Liquid biopsy based BRAF L597Q ddPCR testing was a sensitive personalized biomarker predicting the rise of clinically aggressive metastatic disease. Ex vivo drug sensitivity assays with BRAF L597Q mutated cells showed response to MEK/MAPK targeted therapies.

CONCLUSION:

The rare BRAF L597Q mutation may be associated with aggressive tumor behavior in CRC. Liquid biopsy can be used to capture clinically relevant tumor features.

KEYWORDS:

BRAFnonV600E mutations; Colorectal cancer; MEK/MAPK pathway; ctDNA; ex vivo drug screening; liquid biopsy

PMID:
31704811
DOI:
10.21873/anticanres.13791
[Indexed for MEDLINE]

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