An Accurate and Comprehensive Clinical Sequencing Assay for Cancer Targeted and Immunotherapies

Cao, Jingyu; Chen, Lijuan; Li, Heng; Chen, Hui; Yao, Jie; Mu, Shuo; Liu, Wenjin; Zhang, Peng; Cheng, Yu‐Wei; Liu, Binbin; Chen, Donglin; Kang, Hui; Hu, Jinwei; Wang, Aodi; Wang, Weifeng; Yao, Ming; Chrin, Gungwei; Wang, Xiaoting; Zhao, Wei; Li, Lei; Xu, Lei; Guo, Wei; Jia, Jun; Chen, Jianhua; Wang, Kai; Li, Gaofeng; Shi, Weiwei

doi:10.1634/theoncologist.2019-0236

Cited by 73 publications

(81 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The genes were captured and sequenced with a mean depth of 800 × using Illumina NextSeq 500 (Illumina, Inc., San Diego, CA, USA). The procedures followed the steps described by Frampton et al 27 Genomic alterations (GAs) were identified according to previous study 28 .Single nucleotide variants (SNVs) were identified using MuTect (version 1.7, Broad Institute, Cambridge, MA, USA). Insertion-deletions (Indels) were identified using PINDEL (version 0.2.5).…”

Section: Methodsmentioning

confidence: 99%

Comprehensive genomic profile of Chinese lung cancer patients and mutation characteristics of individuals resistant to icotinib/gefitinib

Shang

Liu

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Lung cancer is the leading causes of cancer-related death worldwide. Precise treatment based on next-generation sequencing technology has shown advantages in the diagnosis and treatment of lung cancer. This cohort study included 371 lung cancer patients. The lung cancer subtype was related to the smoking status and sex of the patients. The most common mutated genes were TP53 (62%), EGFR (55%), and KRAS (11%). The mutation frequencies of EGFR, TP53, PIK3CA, NFE2L2, KMT2D, FGFR1, CCND1, and CDKN2A were significantly different between lung adenocarcinoma and lung squamous cell carcinoma. We identified the age-associated mutations in ALK, ERBB2, KMT2D, RBM10, NRAS, NF1, PIK3CA, MET, PBRM1, LRP2, and CDKN2B; smoking-associated mutations in CDKN2A, FAT1, FGFR1, NFE2L2, CCNE1, CCND1, SMARCA4, KEAP1, KMT2C, and STK11; tumor stage-associated mutations in ARFRP1, AURKA, and CBFB; and sex-associated mutations in EGFR. Tumor mutational burden (TMB) is associated with tumor subtype, age, sex, and smoking status. TMB-associated mutations included CDKN2A, LRP1B, LRP2, TP53, and EGFR. EGFR amplification was commonly detected in patients with acquired lcotinib/gefitinib resistance. DNMT3A and NOTCH4 mutations may be associated with the benefit of icotinib/gefitinib treatment.

show abstract

Section: Methodsmentioning

confidence: 99%

Comprehensive genomic profile of Chinese lung cancer patients and mutation characteristics of individuals resistant to icotinib/gefitinib

Shang

Liu

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Comprehensive genomic profiling was performed by next‐generation sequencing with a panel of 450 cancer‐related genes, as previously reported on samples collected from October 2016 to March 2019 [19]. More than 97% samples were from the 3A hospitals (top tier) across China; 24% of all samples were from the south, 26% from the north, 31% from the west, and 19% from the east.…”

Section: Methodsmentioning

confidence: 99%

Genomic Alterations of NTRK, POLE, ERBB2, and Microsatellite Instability Status in Chinese Patients with Colorectal Cancer

Guo

Wang

et al. 2020

The Oncologist

Self Cite

View full text Add to dashboard Cite

Background The increasing molecular characterization of colorectal cancers (CRCs) has spurred the need to look beyond RAS, BRAF, and microsatellite instability (MSI). Genomic alterations, including ERBB2 amplifications and mutations, POLE mutations, MSI, and NTRK1–3 fusions, have emerged as targets for matched therapies. We sought to study a clinically annotated Chinese cohort of CRC subjected to genomic profiling to explore relative target frequencies. Methods Tumor and matched whole blood were collected from 609 Chinese patients with CRC. Extracted DNA was analyzed for all classes of genomic alterations across 450 cancer‐related genes, including single‐nucleotide variations (SNVs), short and long insertions and deletions (indels), copy number variations, and gene rearrangements. Next‐generation sequencing–based computational algorithms also determined tumor mutational burden and MSI status. Results Alterations in TP53 (76%), APC (72%), and KRAS (46%) were common in Chinese patients with CRC. For the first time, the prevalence of NTRK gene fusion was observed to be around 7% in the MSI‐high CRC cohort. Across the cohort, MSI was found in 9%, ERBB2 amplification in 3%, and POLE pathogenic mutation in 1.5% of patients. Such results mostly parallel frequencies observed in Western patients. However, POLE existed at a higher frequency and was associated with large tumor T‐cell infiltration. Conclusion Comparing to the Western counterparts, POLE mutations were increased in our cohort. The prevalence of NTRK gene fusion was around 7% in the MSI‐high CRC cohort. Increased adoption of molecular profiling in Asian patients is essential for the improvement of therapeutic outcomes. Implications for Practice The increasing use of genomic profiling assays in colorectal cancer (CRC) has allowed for the identification of a higher number of patient subsets benefiting from matched therapies. With an increase in the number of therapies, assays simultaneously evaluating all candidate biomarkers are critical. The results of this study provide an early support for the feasibility and utility of genomic profiling in Chinese patients with CRC.

show abstract

“…Other smaller DNA-targeted panels have been evaluated on FFPE clinical samples: a good concordance with gold standard methods and a good sensitivity and specificity was observed, the overall amount of DNA input required is usually equal to 50–250 ng [ 47 , 48 , 49 , 50 , 51 , 52 ]. Moreover, this approach has also been specifically tested on critical clinical samples like Endobronchial Ultrasound Guided Transbronchial Needle Aspiration (EBUS).…”

Section: Data Sourcesmentioning

confidence: 99%

Next Generation Sequencing for Gene Fusion Analysis in Lung Cancer: A Literature Review

2020

View full text Add to dashboard Cite

Gene fusions have a pivotal role in non-small cell lung cancer (NSCLC) precision medicine. Several techniques can be used, from fluorescence in situ hybridization and immunohistochemistry to next generation sequencing (NGS). Although several NGS panels are available, gene fusion testing presents more technical challenges than other variants. This is a PubMed-based narrative review aiming to summarize NGS approaches for gene fusion analysis and their performance on NSCLC clinical samples. The analysis can be performed at DNA or RNA levels, using different target enrichment (hybrid-capture or amplicon-based) and sequencing chemistries, with both custom and commercially available panels. DNA sequencing evaluates different alteration types simultaneously, but large introns and repetitive sequences can impact on the performance and it does not discriminate between expressed and unexpressed gene fusions. RNA-based targeted approach analyses and quantifies directly fusion transcripts and is more accurate than DNA panels on tumor tissue, but it can be limited by RNA quality and quantity. On liquid biopsy, satisfying data have been published on circulating tumor DNA hybrid-capture panels. There is not a perfect method for gene fusion analysis, but NGS approaches, though still needing a complete standardization and optimization, present several advantages for the clinical practice.

show abstract

An Accurate and Comprehensive Clinical Sequencing Assay for Cancer Targeted and Immunotherapies

Cited by 73 publications

References 28 publications

Comprehensive genomic profile of Chinese lung cancer patients and mutation characteristics of individuals resistant to icotinib/gefitinib

Comprehensive genomic profile of Chinese lung cancer patients and mutation characteristics of individuals resistant to icotinib/gefitinib

Genomic Alterations of NTRK, POLE, ERBB2, and Microsatellite Instability Status in Chinese Patients with Colorectal Cancer

Next Generation Sequencing for Gene Fusion Analysis in Lung Cancer: A Literature Review

Contact Info

Product

Resources

About