Concordance Study of a 520-Gene Next-Generation Sequencing-Based Genomic Profiling Assay of Tissue and Plasma Samples

Wang, Minghui; Chen, Xianshan; Dai, Yongmei; Wu, Duoguang; Liu, Fang; Yang, Zheng; Song, Baozhi; Xie, Li; Yang, Liangwei; Zhao, Weidi; Zhang, Chenxu; Shen, Weitao; Fan, Chengjuan; Teng, Chong; Zhao, Xue; Gao, Naisheng; Shang, Di; Zhao, Guofang; Xin, Tao

doi:10.1007/s40291-022-00579-1

Cited by 18 publications

(11 citation statements)

References 28 publications

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“…DNA was extracted from FFPE tumor tissues using the QIAamp DNA FFPE tissue kit (Qiagen, Hilden, Germany), following the manufacturer’s instructions. Capture-based targeted sequencing was performed using a 520-gene panel (OncoScreen ® Plus, Burning Rock Biotech, Guangzhou, China) as previously described [ 38 , 39 , 40 ]. Data analyses, including variants calling and interpretation, copy number variation, TMB estimation, and MSI status assessment, were carried out using standardized pipelines based on the methods described previously [ 40 ].…”

Section: Methodsmentioning

confidence: 99%

Immunologic Signatures across Molecular Subtypes and Potential Biomarkers for Sub-Stratification in Endometrial Cancer

Jiang

Cao

et al. 2023

IJMS

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Current molecular classification approaches for endometrial cancer (EC) often employ multiple testing platforms. Some subtypes still lack univocal prognostic significance, highlighting the need for risk sub-stratification. The tumor immune microenvironment (TIME) is associated with tumor progression and prognosis. We sought to investigate the feasibility of classifying EC via DNA sequencing and interrogate immunologic signatures and prognostic markers across and within subtypes, respectively. Formalin-fixed paraffin-embedding (FFPE) samples from 50 EC patients underwent targeted DNA and RNA sequencing, and multiplex immunofluorescence assay for TIME. DNA sequencing classified 10%, 20%, 52%, and 18% of patients into the subtype of POLE-mutant, microsatellite instability-high (MSI-H), TP53-wt, and TP53-mutant. POLE-mutant tumors expressed the highest T-effector and IFN-γ signature and the lowest innate anti-PD-1 resistance signature among subtypes. TP53-wt revealed a converse enrichment trend for these immunologic signatures. Survival analyses using the Cancer Genome Atlas Uterine Corpus Endometrial Carcinoma (TCGA-UCEC) dataset identified associations of CCR5 (hazard ratio (HR) = 0.71, p = 0.035), TNFRSF14 (HR = 0.58, p = 0.028), and IL-10 (HR = 2.5, p = 0.012) with overall survival within MSI-H, TP53-mutant, and TP53-wt subtype, respectively. A TIME comparison between the sub-stratified subgroups of our cohort revealed upregulated tumor infiltration of immune cells in the low-risk subgroups. Our study demonstrates that targeted DNA sequencing is an effective one-stop strategy to classify EC. Immunomodulatory genes may serve as prognostic markers within subtypes.

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Section: Methodsmentioning

confidence: 99%

Immunologic Signatures across Molecular Subtypes and Potential Biomarkers for Sub-Stratification in Endometrial Cancer

Jiang

Cao

et al. 2023

IJMS

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“…The genomic profiling was conducted by a hybridization capture-based NGS assay using a commercial panel consisting of 520 cancer-associated genes (OncoScreen Plus, Burning Rock Biotech), spanning 1.64 Mb of the human genome ( Wang et al, 2022 ). Tissue DNA was fragmented using Covaris M220 (Covaris, MA, United States) followed by end repair, adapter ligation and purification of fragments with sizes between 200 and 400 base pairs.…”

Section: Methodsmentioning

confidence: 99%

Distinct clinical pattern of colorectal cancer patients with POLE mutations: A retrospective study on real-world data

et al. 2022

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Objective: Studies have demonstrated an association between somatic POLE exonuclease domain mutations (EDMs) and the prognosis of colorectal cancer (CRC). However, the prognostic value of POLE non-EDMs remains unclear. This retrospective study aimed to explore the possible relationships between POLE mutation subtypes and CRC prognosis.Methods: The 272 CRC patients from the First Affiliated Hospital of Zhengzhou University (ZZ cohort) and 499 CRC patients from The Cancer Genome Atlas database (TCGA cohort) were retrospectively collected. The cases were divided into subgroups based on POLE mutation sites and microsatellite instability (MSI) status. The continuous variables were compared among three subgroups with Kruskal-Wallis tests. Pairwise comparisons between three groups were performed by Bonferroni correction method, and adjusted p < 0.05 was considered statistically significant. The categorical variables were compared with Chi-square test and Fisher’s exact test. The Kaplan—Meier curves and Cox regression models were conducted to evaluate prognostic values of POLE mutations.Results: In the ZZ cohort, POLE EDMs (2.6%) were significantly associated with younger age (p = 0.018) and localized in the left colon (p = 0.001). POLE non-EDMs were significantly associated with MSI-high status (p < 0.001) and localization in the right colon (p = 0.001). In the TCGA cohort, the tumor mutation burden (TMB) of both POLE EDM tumors (p < 0.001) and POLE non-EDM tumors (p < 0.001) was significantly higher than that of POLE wild-type (WT) tumors. A similar trend was observed in the ZZ cohort, although there were no significant differences. In the ZZ cohort, the POLE EDM group had higher progression-free survival (PFS) (p = 0.002) and overall survival (OS) (p = 0.042) than the POLE non-EDM group and POLE WT group. We also report one CRC patient harboring a germline POLE mutation who received camrelizumab and exhibited long-term stable disease.Conclusion: Both POLE-EDMs and POLE non-EDMs were associated with significantly increased TMB in CRC and may be biomarkers for CRC treatment and prognosis. Current evidence does not support an effect of POLE non-EDMs on PFS and OS. A significant association between POLE EDMs and improved PFS and OS may exist, but future studies with larger sample sizes are needed. Entire coding region of the POLE gene should be screened.

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“…Genetic alterations were detected by OncoScreen assay, 18 which surveys the following 10 SWI/SNF subunits: ARID1A, SMARCA4, ARID1B, ARID2, PBRM1, SMARCA2, SMARCB1, SMARCD1, BRD7, and BCL11A. SWI/SNF‐mut was defined as having a mutation in at least one of these subunits; otherwise, SWI/SNF‐wt was defined.…”

Section: Methodsmentioning

confidence: 99%

Correlations of switch/sucrose nonfermentable complex mutations with clinical outcomes in advanced non–small cell lung cancer

Chang

Bai

et al. 2022

Thoracic Cancer

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Background: The switch/sucrose nonfermentable complex mutations (SWI/SNF-mut) are common in non-small cell lung cancer (NSCLC). However, the association of SWI/SNF-mut with the clinical outcomes of immune checkpoint inhibitors (ICIs), particularly of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), has not been established. Methods: We retrospectively collected data of patients at Cancer Hospital Chinese Academy of Medical Sciences. Patients with advanced NSCLC who received programmed cell death protein-1 or programmed cell death ligand 1 (PD-[L]1) inhibitors were included in cohort 1 and those with EGFR mutations (EGFR-mutant) received EGFR-TKIs monotherapy were included in cohort 2. Two reported Memorial Sloan-Kettering Cancer Center (MSKCC) cohorts received immunotherapy alone used as the validation for cohort 1. We analyzed the relationship between SWI/SNF alterations and clinical outcomes in each cohort. Results: In total, 1162 patients were included, of which 230 patients (19.8%) were identified as SWI/SNF-mut with the most common genetic alterations being ARID1A (33.4%) and SMARCA4 (28.3%). In cohort 1 (n = 146), patients with co-mutations of SWI/SNF and Kirsten rat sarcoma oncogene (KRAS) (SWI/SNFmutKRASmut, n = 18) had significantly prolonged progression-free survival (PFS) (8.6 m vs. 1.9 m; hazard ratio [HR], 0.31; 95% confidence intervals [CI], 0.11-0.83; p = 0.032) to PD-(L)1 inhibitors monotherapy, which was consistent with the MSKCC cohorts (not reach [NR] vs. 6.3 m; HR, 0.36, 95% CI, 0.15-0.82; p = 0.016). In cohort 2 (n = 205), ARID1A-mut (n = 16) was associated with improved PFS after EGFR-TKIs (20.6 m vs. 11.2 m; HR, 0.47, 95% CI, 0.27-0.94; p = 0.023). Conclusions: In advanced NSCLC, patients with SWI/SNFmutKRASmut seem to benefit more from ICIs. Furthermore, ARID1A-mut may provide a protective effect to EGFR-TKIs in EGFR-mutant patients. However, this is a retrospective singleinstitution analysis that requires further validation by large prospective studies.K E Y W O R D S epidermal growth factor receptor, immune checkpoint inhibitors, non-small cell lung cancer, SWI/SNF, tyrosine kinase inhibitors

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Concordance Study of a 520-Gene Next-Generation Sequencing-Based Genomic Profiling Assay of Tissue and Plasma Samples

Cited by 18 publications

References 28 publications

Immunologic Signatures across Molecular Subtypes and Potential Biomarkers for Sub-Stratification in Endometrial Cancer

Immunologic Signatures across Molecular Subtypes and Potential Biomarkers for Sub-Stratification in Endometrial Cancer

Distinct clinical pattern of colorectal cancer patients with POLE mutations: A retrospective study on real-world data

Correlations of switch/sucrose nonfermentable complex mutations with clinical outcomes in advanced non–small cell lung cancer

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