Development and Validation of a Scalable Next-Generation Sequencing System for Assessing Relevant Somatic Variants in Solid Tumors
Next-generation sequencing (NGS) has enabled genome-wide personalized oncology efforts at centers and companies with the specialty expertise and infrastructure required to identify and prioritize actionable variants. Such approaches are not scalable, preventing widespread adoption. Likewise, most ta...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2015-04-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558615000445 |
| _version_ | 1817968187095908352 |
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| author | Daniel H. Hovelson Andrew S. McDaniel Andi K. Cani Bryan Johnson Kate Rhodes Paul D. Williams Santhoshi Bandla Geoffrey Bien Paul Choppa Fiona Hyland Rajesh Gottimukkala Guoying Liu Manimozhi Manivannan Jeoffrey Schageman Efren Ballesteros-Villagrana Catherine S. Grasso Michael J. Quist Venkata Yadati Anmol Amin Javed Siddiqui Bryan L. Betz Karen E. Knudsen Kathleen A. Cooney Felix Y. Feng Michael H. Roh Peter S. Nelson Chia-Jen Liu David G. Beer Peter Wyngaard Arul M. Chinnaiyan Seth Sadis Daniel R. Rhodes Scott A. Tomlins |
| author_facet | Daniel H. Hovelson Andrew S. McDaniel Andi K. Cani Bryan Johnson Kate Rhodes Paul D. Williams Santhoshi Bandla Geoffrey Bien Paul Choppa Fiona Hyland Rajesh Gottimukkala Guoying Liu Manimozhi Manivannan Jeoffrey Schageman Efren Ballesteros-Villagrana Catherine S. Grasso Michael J. Quist Venkata Yadati Anmol Amin Javed Siddiqui Bryan L. Betz Karen E. Knudsen Kathleen A. Cooney Felix Y. Feng Michael H. Roh Peter S. Nelson Chia-Jen Liu David G. Beer Peter Wyngaard Arul M. Chinnaiyan Seth Sadis Daniel R. Rhodes Scott A. Tomlins |
| author_sort | Daniel H. Hovelson |
| collection | DOAJ |
| description | Next-generation sequencing (NGS) has enabled genome-wide personalized oncology efforts at centers and companies with the specialty expertise and infrastructure required to identify and prioritize actionable variants. Such approaches are not scalable, preventing widespread adoption. Likewise, most targeted NGS approaches fail to assess key relevant genomic alteration classes. To address these challenges, we predefined the catalog of relevant solid tumor somatic genome variants (gain-of-function or loss-of-function mutations, high-level copy number alterations, and gene fusions) through comprehensive bioinformatics analysis of >700,000 samples. To detect these variants, we developed the Oncomine Comprehensive Panel (OCP), an integrative NGS-based assay [compatible with <20 ng of DNA/RNA from formalin-fixed paraffin-embedded (FFPE) tissues], coupled with an informatics pipeline to specifically identify relevant predefined variants and created a knowledge base of related potential treatments, current practice guidelines, and open clinical trials. We validated OCP using molecular standards and more than 300 FFPE tumor samples, achieving >95% accuracy for KRAS, epidermal growth factor receptor, and BRAF mutation detection as well as for ALK and TMPRSS2:ERG gene fusions. Associating positive variants with potential targeted treatments demonstrated that 6% to 42% of profiled samples (depending on cancer type) harbored alterations beyond routine molecular testing that were associated with approved or guideline-referenced therapies. As a translational research tool, OCP identified adaptive CTNNB1 amplifications/mutations in treated prostate cancers. Through predefining somatic variants in solid tumors and compiling associated potential treatment strategies, OCP represents a simplified, broadly applicable targeted NGS system with the potential to advance precision oncology efforts. |
| first_indexed | 2024-04-13T20:05:29Z |
| format | Article |
| id | doaj.art-e35c27ad1bb744a8a1d6afe2cf1f770b |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-04-13T20:05:29Z |
| publishDate | 2015-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-e35c27ad1bb744a8a1d6afe2cf1f770b2022-12-22T02:32:01ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022015-04-0117438539910.1016/j.neo.2015.03.004Development and Validation of a Scalable Next-Generation Sequencing System for Assessing Relevant Somatic Variants in Solid TumorsDaniel H. Hovelson0Andrew S. McDaniel1Andi K. Cani2Bryan Johnson3Kate Rhodes4Paul D. Williams5Santhoshi Bandla6Geoffrey Bien7Paul Choppa8Fiona Hyland9Rajesh Gottimukkala10Guoying Liu11Manimozhi Manivannan12Jeoffrey Schageman13Efren Ballesteros-Villagrana14Catherine S. Grasso15Michael J. Quist16Venkata Yadati17Anmol Amin18Javed Siddiqui19Bryan L. Betz20Karen E. Knudsen21Kathleen A. Cooney22Felix Y. Feng23Michael H. Roh24Peter S. Nelson25Chia-Jen Liu26David G. Beer27Peter Wyngaard28Arul M. Chinnaiyan29Seth Sadis30Daniel R. Rhodes31Scott A. Tomlins32Michigan Center for Translational Pathology, Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI, USADepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI, USADepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI, USAThermo Fisher Scientific, Ann Arbor, MI, USAThermo Fisher Scientific, Ann Arbor, MI, USAThermo Fisher Scientific, Ann Arbor, MI, USAThermo Fisher Scientific, Ann Arbor, MI, USAThermo Fisher Scientific, Ann Arbor, MI, USAThermo Fisher Scientific, Ann Arbor, MI, USAThermo Fisher Scientific, Ann Arbor, MI, USAThermo Fisher Scientific, Ann Arbor, MI, USAThermo Fisher Scientific, Ann Arbor, MI, USAThermo Fisher Scientific, Ann Arbor, MI, USAThermo Fisher Scientific, Ann Arbor, MI, USAThermo Fisher Scientific, Ann Arbor, MI, USADepartment of Pathology, Oregon Health and Sciences University, Portland, OR, USADepartment of Pathology, Oregon Health and Sciences University, Portland, OR, USADepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI, USADepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI, USADepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI, USADepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI, USADepartment of Cancer Biology, Thomas Jefferson University, Philadelphia, PA, USADepartment of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USADepartment of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI, USADepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI, USADivision of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, USADepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI, USADepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI, USAThermo Fisher Scientific, Ann Arbor, MI, USAMichigan Center for Translational Pathology, Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI, USAThermo Fisher Scientific, Ann Arbor, MI, USADepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI, USADepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI, USANext-generation sequencing (NGS) has enabled genome-wide personalized oncology efforts at centers and companies with the specialty expertise and infrastructure required to identify and prioritize actionable variants. Such approaches are not scalable, preventing widespread adoption. Likewise, most targeted NGS approaches fail to assess key relevant genomic alteration classes. To address these challenges, we predefined the catalog of relevant solid tumor somatic genome variants (gain-of-function or loss-of-function mutations, high-level copy number alterations, and gene fusions) through comprehensive bioinformatics analysis of >700,000 samples. To detect these variants, we developed the Oncomine Comprehensive Panel (OCP), an integrative NGS-based assay [compatible with <20 ng of DNA/RNA from formalin-fixed paraffin-embedded (FFPE) tissues], coupled with an informatics pipeline to specifically identify relevant predefined variants and created a knowledge base of related potential treatments, current practice guidelines, and open clinical trials. We validated OCP using molecular standards and more than 300 FFPE tumor samples, achieving >95% accuracy for KRAS, epidermal growth factor receptor, and BRAF mutation detection as well as for ALK and TMPRSS2:ERG gene fusions. Associating positive variants with potential targeted treatments demonstrated that 6% to 42% of profiled samples (depending on cancer type) harbored alterations beyond routine molecular testing that were associated with approved or guideline-referenced therapies. As a translational research tool, OCP identified adaptive CTNNB1 amplifications/mutations in treated prostate cancers. Through predefining somatic variants in solid tumors and compiling associated potential treatment strategies, OCP represents a simplified, broadly applicable targeted NGS system with the potential to advance precision oncology efforts.http://www.sciencedirect.com/science/article/pii/S1476558615000445 |
| spellingShingle | Daniel H. Hovelson Andrew S. McDaniel Andi K. Cani Bryan Johnson Kate Rhodes Paul D. Williams Santhoshi Bandla Geoffrey Bien Paul Choppa Fiona Hyland Rajesh Gottimukkala Guoying Liu Manimozhi Manivannan Jeoffrey Schageman Efren Ballesteros-Villagrana Catherine S. Grasso Michael J. Quist Venkata Yadati Anmol Amin Javed Siddiqui Bryan L. Betz Karen E. Knudsen Kathleen A. Cooney Felix Y. Feng Michael H. Roh Peter S. Nelson Chia-Jen Liu David G. Beer Peter Wyngaard Arul M. Chinnaiyan Seth Sadis Daniel R. Rhodes Scott A. Tomlins Development and Validation of a Scalable Next-Generation Sequencing System for Assessing Relevant Somatic Variants in Solid Tumors Neoplasia: An International Journal for Oncology Research |
| title | Development and Validation of a Scalable Next-Generation Sequencing System for Assessing Relevant Somatic Variants in Solid Tumors |
| title_full | Development and Validation of a Scalable Next-Generation Sequencing System for Assessing Relevant Somatic Variants in Solid Tumors |
| title_fullStr | Development and Validation of a Scalable Next-Generation Sequencing System for Assessing Relevant Somatic Variants in Solid Tumors |
| title_full_unstemmed | Development and Validation of a Scalable Next-Generation Sequencing System for Assessing Relevant Somatic Variants in Solid Tumors |
| title_short | Development and Validation of a Scalable Next-Generation Sequencing System for Assessing Relevant Somatic Variants in Solid Tumors |
| title_sort | development and validation of a scalable next generation sequencing system for assessing relevant somatic variants in solid tumors |
| url | http://www.sciencedirect.com/science/article/pii/S1476558615000445 |
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