Introduction
Tumorigenesis involves in many somatic mutations, most of which are random. Generally, hundreds of genes are thought to be associated with oncogenesis progression and have high mutation rates. Digging deeper into the cancer genome can help to understand the molecular mechanisms of tumorigenesis and provide guidance for the prevention, treatment and prognosis strategies.
The main drawback of single gene tests is their limited scope. Each test requires time, resources and samples. As the number of tests increases, the feasibility of performing all tests effectively decreases. Next-generation sequencing (NGS) technology, which can sequence millions of DNA molecules simultaneously and in parallel, has rapidly attracted the attention of researchers over the past decade. Multiplexed approaches have been developed to test a selected set of genes, whole exomes or genomes in a single assay.
What is the NGS Gene Panel and how does it work?
Gene panels make NGS and data analysis more economical, flexible and efficient. The use of them can improve the detection of genetically heterogeneous disorders and diseases with overlapping phenotypes, while assessing multiple potential genetic causes of suspicion. Most of the currently commercially available panels use two target enrichment strategies. The hybridization capture enrichment employs oligonucleotide probes (typically 60-100 bp oligonucleotides) specific to selected sequences, to enrich the corresponding DNA for subsequent sequencing in the hybridization reactions. Amplicon-based enrichment method relies on synthetic PCR primers to generate copies of targeted DNA sequences, which is easily affected by the quality of DNA and amplification efficiency. A variety of targeting enrichment kits have been developed to monitor the onset or recurrence of cancer, tumor burden and evolution, including the development of therapeutic resistance.
Cancer Risk Assessment Using Genetic Panel Testing
High penetrance of hereditary cancer susceptibility genes in hereditary breast cancer accounts for approximately 5-10% of cases, and 20% of cases are thought to be familial; therefore, some of them cannot be attributed to a single inherited mutation, but also include polygenic inheritance, etc. As cancer-related mutations are cumulatively being identified and characterized, the variety of cancer gene panels is increasing. NGS Panels and sequencing allow rapid evaluation and study of hundreds of known and potential genetic cancer mutations. Combining with pathological phenotypic analysis, they help to achieve more accurate risk stratification and cancer treatment development.
Rare Cancer Mutation Research Using Genetic Panel Testing
Rare cancers (RCs) research often lacks preclinical models for evaluation and studying pathogenesis, making it difficult to find effective treatments. The whole exome sequencing panel can detect pathogenic variants in almost all coding regions of the genome, covering more than 22,000 protein-coding genes, as well as several untranslated regions and intron-exon boundaries. Panels aim to improve the coverage of medically relevant genes at low cost, boosting the identification of structural variants, tandem repeats and pathogenic variants. The whole exome sequencing panel has been used to identify and evaluate rare mutations associated with colorectal cancer, pancreatic cancer, and melanoma, etc.
