Cancer Diagnostics: Targeted Gene Panels for Next Generation of Sequencing
Genome-wide next-generation of sequencing (NGS), such as whole genome sequencing (WGS) and whole exome sequencing (WES) has been used for germline and somatic mutation studies. However, due to the high cost and turnaround time, these NGS methods have not been widely used clinically for cancer diagnostics. On contrast, NGS using targeted gene panels is popular for simultaneous gene mutation detection across different cancer types, including lung cancer, colon cancer, breast cancer, and many others.
The Advantage of NGS Using Targeted Gene Panels
The gene panels contain the known genes whose mutations are associated with certain types of cancer. Targeted sequencing using these cancer gene panels reduce the sequencing depth by 500- to 1000-fold and improve sequencing sensitivity for variant allele frequency (VAF) from 20 to 25% for Sanger sequencing to 5% for NGS. In addition, thousands of samples can be processed for a single run and results are available within 1 to 2 days. While one can argue that only limited information is obtained from targeted gene panel NGS, not all the sequencing information is needed to get clinically relevant data. Multiple gene panels are designed to provide necessary information needed for special clinical diagnostics.
CLIA-certified Pan Cancer Panel NGS for ctDNA and FFPE samples
All the clinical testing performed on human (except for clinical trials and basic research) in the United States are regulated by federal regulatory Standards, CLIA (Clinical Laboratory Improvement Amendments). With the CLIA-certified Optiseq pan-cancer panel, more than 2900 mutation positions (hotspots) within 65 genes can be detected at as low as 1% VAF from circulating tumor DNA (ctDNA) or formalin-fixed paraffin-embedded (FFPE) samples, covering mutations commonly seen in different cancer types. From this panel test report, oncologists learn accurate and actionable information to guide therapies for advanced cancer patients.
XNA technology for targeted gene panel achieves sensitivity at 0.25% VAF
General gene panels reach detection at 5% VAF sensitivity, addition of XNA technology allows detection limit to go down to 0.25% VAF, enriching mutations by 30-fold and reducing sequencing depth. XNA technology selectively amplifies the mutant sequence while suppressing the wildtype sequence amplification, thereby enriching rare mutations in cancer tissue samples. With the designed Opti-seq NGS cancer Nano Panel V2, mutations in 13 amplicons and 17 hotspots of 7 genes can be easily detected without regular deep sequencing.
Next-generation sequencing (NGS) is a powerful tool that has seen a fast increase in clinical labs although only a few NGS tests have been approved by the FDA. However, there have been a lot of debate on if variants from NGS sequencing should be confirmed either by Sanger sequencing, the gold standard, or other techniques such as quantitative PCR, or the combination, or other methods.
Eighty five percent of the lung cancer patients are non-small cell lung cancer (NSCLC) patients. Among this population, patients with exon 19 deletion and L858R mutations respond well to the first (such as erlotinib and gefitinib) and second generation (such as afatinib and dacomitinib) of tyrosine kinase inhibitors (TKIs). However, all the respondents develop resistance after 9 to 14-month period and more than 50% of the resistance cases are due to the single point mutation at exon 20, T790M.
linkedinfacebooktwitterColorectal cancer (CRC), including colon and rectum cancer, is the third most common cancer in the world and the third in the US as well. American Cancer Society (ACS) estimates that there are 97,220 and 43,030 new cases in 2018 for colon and...
linkedin facebook twitter When mutated, oncogenes can convert normal cells to cancer cells. BRAF is one of the oncogenes that controls transduction of chemical signal from outside the cells to nucleus. As a member of the RAS/MAPK pathway, the BRAF gene product, the...
linkedinfacebooktwitterMolecular Diagnostics has evolved over the years and the numerous benefits it has to offer has earned people’s attention irrespective of the expensive procedures it included. Quicker turnaround times, improved sensitivities, increased accuracy...
linkedinfacebooktwitterAt a pathology lab, a researcher is working on a patient’s blood sample to extract cell-free DNA to find the potential diagnostic biomarker for cancers. Using the current DNA sequencing techniques such as next-generation sequencing (NGS) or...