Genomic profiling of NSCLC tumors with the TruSight oncology 500 assay provides broad coverage of clinically actionable genomic alterations and detection of known and novel associations between genomic alterations, TMB, and PD-L1
IntroductionMatching patients to an effective targeted therapy or immunotherapy is a challenge for advanced and metastatic non-small cell lung cancer (NSCLC), especially when relying on assays that test one marker at a time. Unlike traditional single marker tests, comprehensive genomic profiling (CG...
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| Format: | Article |
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Frontiers Media S.A.
2024-11-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2024.1473327/full |
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| author | Zachary D. Wallen Mary K. Nesline Marni Tierno Alison Roos Erica Schnettler Hatim Husain Pratheesh Sathyan Brian Caveney Marcia Eisenberg Eric A. Severson Shakti H. Ramkissoon Shakti H. Ramkissoon |
| author_facet | Zachary D. Wallen Mary K. Nesline Marni Tierno Alison Roos Erica Schnettler Hatim Husain Pratheesh Sathyan Brian Caveney Marcia Eisenberg Eric A. Severson Shakti H. Ramkissoon Shakti H. Ramkissoon |
| author_sort | Zachary D. Wallen |
| collection | DOAJ |
| description | IntroductionMatching patients to an effective targeted therapy or immunotherapy is a challenge for advanced and metastatic non-small cell lung cancer (NSCLC), especially when relying on assays that test one marker at a time. Unlike traditional single marker tests, comprehensive genomic profiling (CGP) can simultaneously assess NSCLC tumors for hundreds of genomic biomarkers and markers for immunotherapy response, leading to quicker and more precise matches to therapeutics.MethodsIn this study, we performed CGP on 7,606 patients with advanced or metastatic NSCLC using the Illumina TruSight Oncology 500 (TSO 500) CGP assay to show its coverage and utility in detecting known and novel features of NSCLC.ResultsTesting revealed distinct genomic profiles of lung adenocarcinoma and squamous cell carcinomas and detected variants with a current targeted therapy or clinical trial in >72% of patient tumors. Known associations between genomic alterations and immunotherapy markers were observed including significantly lower TMB levels in tumors with therapy-associated alterations and significantly higher PD-L1 levels in tumors with ALK, MET, BRAF, or ROS1 driver mutations. Co-occurrence analysis followed by network analysis with gene module detection revealed known and novel co-occurrences between genomic alterations. Further, certain modules of genes with co-occurring genomic alterations had dose-dependent relationships with histology and increasing or decreasing levels of PD-L1 and TMB, suggesting a complex relationship between PD-L1, TMB, and genomic alterations in these gene modules.DiscussionThis study is the largest clinical study to date utilizing the TSO 500. It provides an opportunity to further characterize the landscape of NSCLC using this newer technology and show its clinical utility in detecting known and novel facets of NSCLC to inform treatment decision-making. |
| format | Article |
| id | doaj-art-7da83e2d387c42eea5c96dbc1c70b4e0 |
| institution | Kabale University |
| issn | 2234-943X |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj-art-7da83e2d387c42eea5c96dbc1c70b4e02024-11-27T05:10:23ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2024-11-011410.3389/fonc.2024.14733271473327Genomic profiling of NSCLC tumors with the TruSight oncology 500 assay provides broad coverage of clinically actionable genomic alterations and detection of known and novel associations between genomic alterations, TMB, and PD-L1Zachary D. Wallen0Mary K. Nesline1Marni Tierno2Alison Roos3Erica Schnettler4Hatim Husain5Pratheesh Sathyan6Brian Caveney7Marcia Eisenberg8Eric A. Severson9Shakti H. Ramkissoon10Shakti H. Ramkissoon11Labcorp Oncology, Durham, NC, United StatesLabcorp Oncology, Durham, NC, United StatesIllumina, San Diego, CA, United StatesIllumina, San Diego, CA, United StatesIllumina, San Diego, CA, United StatesMoores Cancer Center at UC San Diego Health, La Jolla, CA, United StatesIllumina, San Diego, CA, United StatesLabcorp, Burlington, NC, United StatesLabcorp, Burlington, NC, United StatesLabcorp Oncology, Durham, NC, United StatesLabcorp Oncology, Durham, NC, United StatesWake Forest Comprehensive Cancer Center, Wake Forest School of Medicine, Department of Pathology, Winston-Salem, NC, United StatesIntroductionMatching patients to an effective targeted therapy or immunotherapy is a challenge for advanced and metastatic non-small cell lung cancer (NSCLC), especially when relying on assays that test one marker at a time. Unlike traditional single marker tests, comprehensive genomic profiling (CGP) can simultaneously assess NSCLC tumors for hundreds of genomic biomarkers and markers for immunotherapy response, leading to quicker and more precise matches to therapeutics.MethodsIn this study, we performed CGP on 7,606 patients with advanced or metastatic NSCLC using the Illumina TruSight Oncology 500 (TSO 500) CGP assay to show its coverage and utility in detecting known and novel features of NSCLC.ResultsTesting revealed distinct genomic profiles of lung adenocarcinoma and squamous cell carcinomas and detected variants with a current targeted therapy or clinical trial in >72% of patient tumors. Known associations between genomic alterations and immunotherapy markers were observed including significantly lower TMB levels in tumors with therapy-associated alterations and significantly higher PD-L1 levels in tumors with ALK, MET, BRAF, or ROS1 driver mutations. Co-occurrence analysis followed by network analysis with gene module detection revealed known and novel co-occurrences between genomic alterations. Further, certain modules of genes with co-occurring genomic alterations had dose-dependent relationships with histology and increasing or decreasing levels of PD-L1 and TMB, suggesting a complex relationship between PD-L1, TMB, and genomic alterations in these gene modules.DiscussionThis study is the largest clinical study to date utilizing the TSO 500. It provides an opportunity to further characterize the landscape of NSCLC using this newer technology and show its clinical utility in detecting known and novel facets of NSCLC to inform treatment decision-making.https://www.frontiersin.org/articles/10.3389/fonc.2024.1473327/fullnon-small cell lung cancergenomic profilingimmune checkpoint inhibitorsTMBPD-L1clinical utility |
| spellingShingle | Zachary D. Wallen Mary K. Nesline Marni Tierno Alison Roos Erica Schnettler Hatim Husain Pratheesh Sathyan Brian Caveney Marcia Eisenberg Eric A. Severson Shakti H. Ramkissoon Shakti H. Ramkissoon Genomic profiling of NSCLC tumors with the TruSight oncology 500 assay provides broad coverage of clinically actionable genomic alterations and detection of known and novel associations between genomic alterations, TMB, and PD-L1 Frontiers in Oncology non-small cell lung cancer genomic profiling immune checkpoint inhibitors TMB PD-L1 clinical utility |
| title | Genomic profiling of NSCLC tumors with the TruSight oncology 500 assay provides broad coverage of clinically actionable genomic alterations and detection of known and novel associations between genomic alterations, TMB, and PD-L1 |
| title_full | Genomic profiling of NSCLC tumors with the TruSight oncology 500 assay provides broad coverage of clinically actionable genomic alterations and detection of known and novel associations between genomic alterations, TMB, and PD-L1 |
| title_fullStr | Genomic profiling of NSCLC tumors with the TruSight oncology 500 assay provides broad coverage of clinically actionable genomic alterations and detection of known and novel associations between genomic alterations, TMB, and PD-L1 |
| title_full_unstemmed | Genomic profiling of NSCLC tumors with the TruSight oncology 500 assay provides broad coverage of clinically actionable genomic alterations and detection of known and novel associations between genomic alterations, TMB, and PD-L1 |
| title_short | Genomic profiling of NSCLC tumors with the TruSight oncology 500 assay provides broad coverage of clinically actionable genomic alterations and detection of known and novel associations between genomic alterations, TMB, and PD-L1 |
| title_sort | genomic profiling of nsclc tumors with the trusight oncology 500 assay provides broad coverage of clinically actionable genomic alterations and detection of known and novel associations between genomic alterations tmb and pd l1 |
| topic | non-small cell lung cancer genomic profiling immune checkpoint inhibitors TMB PD-L1 clinical utility |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2024.1473327/full |
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