Synonymous Variants of Potential Significance Identified by a 52-Gene Clinical Sequencing Panel in Non-Small Cell Lung Cancer.
Next-generation sequencing (NGS) is routinely used for lung cancer genomic profiling to identify known, actionable, non-synonymous driver mutations. Recent findings suggest that synonymous variants may also be cancer drivers. We analyzed genomic data and clinical outcomes for patients (n = 353) with non-small cell lung cancer (NSCLC) sequenced with the Oncomine Focus 52-gene NGS panel (ThermoFisher Scientific, Waltham, MA, USA) at the Saint John Regional Hospital in New Brunswick, Canada, from January 2019 to January 2023. KRAS was the most commonly mutated gene in this cohort from Saint John, New Brunswick, with a higher prevalence than reported in other populations. Several novel synonymous variants were identified, including in ALK, EGFR, FGFR2, FGFR3, MYC, NF1, NRAS, and PIK3CA, with potential effects on MAPK/ERK and PI3K/AKT signaling. This cohort demonstrates both expected and distinct genomic features, including novel synonymous variants in oncogenic pathways. These findings suggest regional variation in NSCLC genomics and support further study of synonymous variants in disease progression.
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21
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Immune-Related Adverse Events and Outcomes in Patients with Advanced Non–Small Cell Lung Cancer: A Predictive Marker of Efficacy?
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9
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38
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Molecular Biologic Staging of Lung Cancer
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710
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814
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MicroRNA Signature Predicts Survival and Relapse in Lung Cancer
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7
- 10.2217/fon-2017-0240
- Jun 28, 2017
- Future Oncology
afatinib combination EGFR non-small
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24
- 10.1016/j.jtho.2019.05.019
- Nov 20, 2019
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Lung Cancer in Italy
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35
- 10.1378/chest.99.6.1328
- Jun 1, 1991
- Chest
Chemotherapy and Survival in Non-Small Cell Lung Cancer: The Old Vexata Questio
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7
- 10.1016/j.jtho.2023.02.020
- May 18, 2023
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Exploiting the Full Potential of Novel Agents Targeting EGFR Exon 20 Insertions in Advanced NSCLC: Next-Generation Sequencing Outperforms Polymerase Chain Reaction–Based Testing
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1
- 10.1200/jco.2020.38.15_suppl.e21502
- May 20, 2020
- Journal of Clinical Oncology
e21502 Background: Liquid biopsy describes the extraction of circulating tumor DNA (ctDNA) from peripheral blood via next-generation-sequencing (NGS). The yield of adding plasma-based NGS to tissue NGS for the detection of Actionable Mutations (AM) have been reported scarcely and additional “real world” data is needed. Methods: In this retrospective data review, we included patients with non-small cell lung cancer (NSCLC) who had plasma NGS genomic testing ordered between Nov 2014 and July 2019, as part of routine management. Plasma testing was performed using Guardant360 commercial platform and was analyzed for therapeutically AM in: EGFR, ALK, MET, BRCA1, BRCA2, KRAS, ROS1, RET, ERBB2, BRAF, and NTRK2. Results: Over a period of 5 years, 337 samples taken from 279 patients were sent for ctDNA NGS testing. The median age at diagnosis was 73 years [range 36-93, SD:10.4], 51% (N=141) were males and 49% (N=138) were females. Excluding synonymous mutations and variants of unknown significance, 239 samples (71%) and 201 patients (72%) had 705 somatic mutations. Of them, 36% (N=254) were therapeutically actionable and were detected in 139 samples (58%), taken from 106 patients (53%). Commonly detected AM were EGFR (N=127; 50%), KRAS (N=61; 24%), BRAF (N=24; 9.5%), MET (N=23; 9%), RET (N=5; 1.9%), BRCA1 (N=5; 1.9%), BRCA2 (N=4; 1.6%), ERBB2 (N=4; 1.6%) and ALK (N=1, 0.4%). None of the samples had mutations in ROS1, NTRK2. One patient had Microsatellite instability (MSI). Common co-occurring mutations were EGFR and BRAF (N=14), EGFR and MET (N=13) and MET and BRAF (N=10) (p<0.001). Common mutually exclusive mutations were KRAS and EGFR (p<0.001). Tissue NGS analysis was performed in 62/106 patients (58%), with AM found in 45 patients (72%). Concordance agreement in AM between plasma and tissue NGS modalities was detected in 39/45 patients (87%) and was demonstrated in EGFR (N=25), KRAS (N=11), BRAF (N=2) and MET (N=1). In the reminder 6 patients (13%), tissue NGS was discordant from their plasma NGS results. In 44/106 patients, for whom tissue sampling was not performed, utilizing plasma NGS increased AM detection yield by 41%. Conclusions: Integration of plasma NGS testing into the routine management of NSCLC patients demonstrated substantial yield of therapeutically targetable mutations detection rate, when tissue NGS was not available.
- Discussion
408
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48-Year-Old Woman With Dyspnea and Chest Pain
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934
- 10.1093/annonc/mds226
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