Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Detection of BRAF splicing variants in plasma-derived cell-free nucleic acids and extracellular vesicles of melanoma patients failing targeted therapy therapies
Oncotarget, Volume 11, No. 44, Year 2020
Notification
URL copied to clipboard!
Description
The analysis of plasma circulating tumour nucleic acids provides a non-invasive approach to assess disease burden and the genetic evolution of tumours in response to therapy. BRAF splicing variants are known to confer melanoma resistance to BRAF inhibitors. We developed a test to screen cell-free RNA (cfRNA) for the presence of BRAF splicing variants. Custom droplet digital PCR assays were designed for the detection of BRAF splicing variants p61, p55, p48 and p41 and then validated using RNA from cell lines carrying these variants. Evaluation of plasma from patients with reported objective response to BRAF/MEK inhibition followed by disease progression was revealed by increased circulating tumour DNA (ctDNA) in 24 of 38 cases at the time of relapse. Circulating BRAF splicing variants were detected in cfRNA from 3 of these 38 patients; two patients carried the BRAF p61 variant and one the p55 variant. In all three cases the presence of the splicing variant was apparent only at the time of progressive disease. BRAF p61 was also detectable in plasma of one of four patients with confirmed BRAF splicing variants in their progressing tumours. Isolation and analysis of RNA from extracellular vesicles (EV) from resistant cell lines and patient plasma demonstrated that BRAF splicing variants are associated with EVs. These findings indicate that in addition to plasma ctDNA, RNA carried by EVs can provide important tumour specific information. © 2020 Clark et al.
Authors & Co-Authors
Khattak, Muhammad Adnan
Australia, Perth
Edith Cowan University
Australia, Perth
The University of Western Australia
Australia, Perth
Fiona Stanley Hospital
Long, Georgina V.
Australia, Sydney
The University of Sydney
Menzies, Alexander M.
Australia, Sydney
The University of Sydney
Millward, Michael J.
Australia, Perth
Edith Cowan University
Australia, Perth
The University of Western Australia
Australia, Perth
Sir Charles Gairdner Hospital
Ziman, Mel
Australia, Perth
Edith Cowan University
Australia, Perth
The University of Western Australia
Gray, Elin Solomonovna
Australia, Perth
Edith Cowan University
Statistics
Citations: 5
Authors: 6
Affiliations: 8
Identifiers
Doi:
10.18632/oncotarget.27790
ISSN:
19492553
Research Areas
Cancer
Genetics And Genomics
Health System And Policy