Genetic alteration andmutation proifling ofcirculating cell-free tumor DNA (cfDNA) fordiagnosis andtargeted therapy ofgastrointestinal stromal tumors
10.1186/s40880-016-0131-1
- Author:
WeixinYan
1
;
AiguoZhang
;
MichaelJPowell
Author Information
1. Robotics Research Institute
- Keywords:
Gastrointestinal stromal tumors;
Liquid biopsy;
Mutations;
Targeted therapy
- From:Chinese Journal of Cancer
2016;35(7):342-349
- CountryChina
- Language:Chinese
-
Abstract:
Gastrointestinal stromal tumors (GISTs) have been recognized as a biologically distinctive type of tumor, different from smooth muscle and neural tumors of the gastrointestinal tract. The identiifcation of genetic aberrations in proto-oncogenes that drive the growth of GISTs is critical for improving the effcacy of cancer therapy by match-ing targeted drugs to speciifc mutations. Research into the oncogenic mechanisms of GISTs has found that these tumors frequently contain activating gene mutations in either platelet-derived growth factor receptor A (PDGFRA) or a receptor tyrosine protein associated with a mast cell growth factor receptor encoded by theKIT gene. Mutant cancer subpopulations have the potential to disrupt durable patient responses to molecularly targeted therapy for GISTs, yet the prevalence and size of subpopulations remain largely unexplored. Detection of the cancer subpopulations that harbor low-frequency mutant alleles of target proto-oncogenes through the use of molecular genetic methods, such as polymerase chain reaction (PCR) target ampliifcation technology, is hampered by the high abundance of wild-type alleles, which limit the sensitivity of detection of these minor mutant alleles. This is especially true in the case of mutant tumor DNA derived “driver” and “drug-resistant” alleles that are present in the circulating cell-free tumor DNA (cfDNA) in the peripheral blood circulation of GIST patients. So-called “liquid biopsy” allows for the dynamic monitor-ing of the patients’ tumor status during treatment using minimally invasive sampling. New methodologies, such as a technology that employs a xenonucleic acid (XNA) clamping probe to block the PCR ampliifcation of wild-type templates, have allowed improved molecular detection of these low-frequency alleles both in tissue biopsy samples and in cfDNA. These new methodologies could be widely applied for minimally invasive molecular testing in the therapeutic management of GISTs.
