A comprehensive next generation sequencing approach identifies colorectal cancer-related genomic alterations. Detection of NCCN recommended genes and other colorectal cancer targeted drug related, hereditary syndrome risk and immunosuppressive efficacy assessment related genes. The assay provides biomarker information to guide personalized medication, genetic risk and prognosis of patients with colorectal cancer.
The mutation rates of KRAS, NRAS, BRAF and PIK3CA are 45.5%, 3.9%, 3.1% and 3.5% respectively in colorectal cancer patients in China. KRAS, NRAS, BRAF mutations are related to poor prognosis of anti-EGFR target therapy. NCCN and other authoritative guidelines clearly require metastatic colorectal cancer patients to detect RAS/BRAF gene mutation before got targeted treatment.The CAPRI GOIM study showed that the efficacy benefit of cetuximab was limited to the high selectivity (KRAS / NRAS / BRAF / PIK3CA) "quadruple wild" population and adverse trends in the mutant population.
About 25% of patients with colorectal cancer have familial clustering, and it has been clear that about 6% of hereditary colorectal cancer is associated with a variety of genetic syndromes. The pathogenicity of genes associated with hereditary colorectal cancer was analyzed by next generation sequencing, whether the patient was hereditary colorectal cancer, providing targeted treatment regimens, and providing important information for relatives.
Microsatellites are short tandem repeat DNA sequences with lengths of 1-6 base pairs. These repeats are widely found in the genome. In general, the frequency of microsatellite DNA in somatic cells is 10-5-10-7. Studies have shown that patients with microsatellite instability are more likely to benefit from PD-1 immunosuppressive agents.
Progression-free survival and overall survival rate compared with patients with dMMR after treatment of Pembrolizumab
After several splitting proliferation, the daughter of tumor cells showing a molecular biology or genetic changes, leading tumor growth rate, invasive ability, sensitivity to the drug, prognosis and etc., differences. As a new tumor marker in the monitoring of the dynamic development of the tumor，ctDNA has a higher sensitivity and specificity, and can be better than the protein markers and imaging predict the dynamic development of the tumor. So ctDNA can be used for cancer early diagnosis, monitoring cancer development process, prognosis and individualized medication guidance.
Studies have shown that ctDNA can reflect tumor recurrence and progression more accurately than imaging and protein CEA markers.
Colorectal cancer targeted therapy related genes marked as red;
Hereditary colorectal cancer related genes marked as blue;
Other cancer targeted therapy related and driver genes marked as White.
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1. Ciardiello, et al. WCGC 2015. Abstract LBA-09
2. Genetics of Colorectal Cancer. NCI. 2015
3. N Engl J Med 2015;372:2509-20
4. Evelyn Kidess-Sigal，Oncotarget, 2016, Vol. 7: 85349-85364
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