Emergence of MET hyper-amplification at progression to MET and BRAF inhibition in colorectal cancer.

ABSTRACT:

Background

Combined MET and BRAF inhibition showed clinical benefit in a patient with rectal cancer carrying BRAF^V600E 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

SUBMITTER: Oddo D 

PROVIDER: S-EPMC5537500 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature