Dataset Information
Emergence of MET hyper-amplification at progression to MET and BRAF inhibition in colorectal cancer.
Ontology highlight
ABSTRACT: Background
Combined MET and BRAF inhibition showed clinical benefit in a patient with rectal cancer carrying BRAFV600E and MET amplification. However after 4 months, acquired resistance emerged and the patient deceased shortly after disease progression. The mechanism of resistance to this drug combination is unknown.Methods
We analysed plasma circulating tumour DNA obtained at progression by exome sequencing and digital PCR. MET gene and mRNA in situ hybridisation analyses in two bioptic specimens obtained at progression were used to confirm the plasma data.Results
We identified in plasma MET gene hyper-amplification as a potential mechanism underlying therapy resistance. Increased MET gene copy and transcript levels were detected in liver and lymph node metastatic biopsies. Finally, transduction of MET in BRAF mutant colorectal cancer cells conferred refractoriness to BRAF and MET inhibition.Conclusions
We identified in a rectal cancer patient MET gene hyper-amplification as mechanism of resistance to dual BRAF and MET inhibition.
SUBMITTER: Oddo D
PROVIDER: S-EPMC5537500 | biostudies-literature | 2017 Jul
REPOSITORIES: biostudies-literature
Publications
Emergence of MET hyper-amplification at progression to MET and BRAF inhibition in colorectal cancer.
British journal of cancer 20170627 3
<h4>Background</h4>Combined MET and BRAF inhibition showed clinical benefit in a patient with rectal cancer carrying BRAF<sup>V600E</sup> and MET amplification. However after 4 months, acquired resistance emerged and the patient deceased shortly after disease progression. The mechanism of resistance to this drug combination is unknown.<h4>Methods</h4>We analysed plasma circulating tumour DNA obtained at progression by exome sequencing and digital PCR. MET gene and mRNA in situ hybridisation anal ...[more]