Detecting gene copy number alterations by Oncomine Comprehensive genomic profiling in a comparative study on FFPE tumor samples
Abstract Copy number alterations (CNAs) play a fundamental role in cancer development and constitute a potential tool for tailored treatments. The CNAs recognition in formalin fixed paraffin embedded (FFPE) material for diagnostic purposes has relied for years mainly on fluorescence in situ hybridiz...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-02-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-025-88494-3 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1823862273221853184 |
|---|---|
| author | Fabio Bozzi Elena Conca Marco Silvestri Gianpaolo Dagrada Alice Ardore Donata Penso Daniele Lorenzini Chiara Costanza Volpi Desirè Viola Trupia Adele Busico Iolanda Capone Federica Perrone Elena Tamborini Andrea Vingiani Luca Agnelli Giancarlo Pruneri |
| author_facet | Fabio Bozzi Elena Conca Marco Silvestri Gianpaolo Dagrada Alice Ardore Donata Penso Daniele Lorenzini Chiara Costanza Volpi Desirè Viola Trupia Adele Busico Iolanda Capone Federica Perrone Elena Tamborini Andrea Vingiani Luca Agnelli Giancarlo Pruneri |
| author_sort | Fabio Bozzi |
| collection | DOAJ |
| description | Abstract Copy number alterations (CNAs) play a fundamental role in cancer development and constitute a potential tool for tailored treatments. The CNAs recognition in formalin fixed paraffin embedded (FFPE) material for diagnostic purposes has relied for years mainly on fluorescence in situ hybridization. The introduction of other procedures, such as Next-Generation Sequencing has dramatically improved CNAs discovery at genome-wide level. The detection of CNAs by NGS in FFPE material is, nonetheless, a complex issue, which still requires validation studies. Herein, the CNAs detection by a widely used NGS assay (Oncomine Comprehensive Assay plus®, OCA+) were evaluated in 14 FFPE samples mirroring diagnostic daily practice and compared to a whole-genome assay. OCA+, a targeted DNA panel, showed lower CNAs detection sensitivity and equal specificity for gains and losses. According to proprietary software pipeline, OCA+ accurately identified gains characterized by CN ≥ 5,2. No significant threshold maximizing the difference between true and false positive losses was found. Orthogonal FISH tests validated seven CNAs characterized by CN gain ≥ 6 or complete loss. Considering the CNAs growing significance in precision medicine, our findings further prompt towards a robust validation of NGS detection in FFPE materials. |
| format | Article |
| id | doaj-art-feac8fdf20cf4deb8481d7084c002a68 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-feac8fdf20cf4deb8481d7084c002a682025-02-09T12:36:32ZengNature PortfolioScientific Reports2045-23222025-02-0115111110.1038/s41598-025-88494-3Detecting gene copy number alterations by Oncomine Comprehensive genomic profiling in a comparative study on FFPE tumor samplesFabio Bozzi0Elena Conca1Marco Silvestri2Gianpaolo Dagrada3Alice Ardore4Donata Penso5Daniele Lorenzini6Chiara Costanza Volpi7Desirè Viola Trupia8Adele Busico9Iolanda Capone10Federica Perrone11Elena Tamborini12Andrea Vingiani13Luca Agnelli14Giancarlo Pruneri15Department of Diagnostic Innovation, Pathology Unit 2, Fondazione IRCCS Istituto Nazionale Dei TumoriDepartment of Diagnostic Innovation, Pathology Unit 2, Fondazione IRCCS Istituto Nazionale Dei TumoriDepartment of Research, Nutrition and Metabolomics, Fondazione IRCCS Istituto Nazionale Dei TumoriDepartment of Diagnostic Innovation, Pathology Unit 2, Fondazione IRCCS Istituto Nazionale Dei TumoriDepartment of Diagnostic Innovation, Pathology Unit 2, Fondazione IRCCS Istituto Nazionale Dei TumoriDepartment of Diagnostic Innovation, Pathology Unit 2, Fondazione IRCCS Istituto Nazionale Dei TumoriDepartment of Diagnostic Innovation, Pathology Unit 2, Fondazione IRCCS Istituto Nazionale Dei TumoriDepartment of Diagnostic Innovation, Pathology Unit 2, Fondazione IRCCS Istituto Nazionale Dei TumoriDepartment of Diagnostic Innovation, Pathology Unit 2, Fondazione IRCCS Istituto Nazionale Dei TumoriDepartment of Diagnostic Innovation, Pathology Unit 2, Fondazione IRCCS Istituto Nazionale Dei TumoriDepartment of Diagnostic Innovation, Pathology Unit 2, Fondazione IRCCS Istituto Nazionale Dei TumoriDepartment of Diagnostic Innovation, Pathology Unit 2, Fondazione IRCCS Istituto Nazionale Dei TumoriDepartment of Diagnostic Innovation, Pathology Unit 2, Fondazione IRCCS Istituto Nazionale Dei TumoriDepartment of Diagnostic Innovation, Pathology Unit 2, Fondazione IRCCS Istituto Nazionale Dei TumoriDepartment of Diagnostic Innovation, Pathology Unit 2, Fondazione IRCCS Istituto Nazionale Dei TumoriDepartment of Diagnostic Innovation, Pathology Unit 2, Fondazione IRCCS Istituto Nazionale Dei TumoriAbstract Copy number alterations (CNAs) play a fundamental role in cancer development and constitute a potential tool for tailored treatments. The CNAs recognition in formalin fixed paraffin embedded (FFPE) material for diagnostic purposes has relied for years mainly on fluorescence in situ hybridization. The introduction of other procedures, such as Next-Generation Sequencing has dramatically improved CNAs discovery at genome-wide level. The detection of CNAs by NGS in FFPE material is, nonetheless, a complex issue, which still requires validation studies. Herein, the CNAs detection by a widely used NGS assay (Oncomine Comprehensive Assay plus®, OCA+) were evaluated in 14 FFPE samples mirroring diagnostic daily practice and compared to a whole-genome assay. OCA+, a targeted DNA panel, showed lower CNAs detection sensitivity and equal specificity for gains and losses. According to proprietary software pipeline, OCA+ accurately identified gains characterized by CN ≥ 5,2. No significant threshold maximizing the difference between true and false positive losses was found. Orthogonal FISH tests validated seven CNAs characterized by CN gain ≥ 6 or complete loss. Considering the CNAs growing significance in precision medicine, our findings further prompt towards a robust validation of NGS detection in FFPE materials.https://doi.org/10.1038/s41598-025-88494-3 |
| spellingShingle | Fabio Bozzi Elena Conca Marco Silvestri Gianpaolo Dagrada Alice Ardore Donata Penso Daniele Lorenzini Chiara Costanza Volpi Desirè Viola Trupia Adele Busico Iolanda Capone Federica Perrone Elena Tamborini Andrea Vingiani Luca Agnelli Giancarlo Pruneri Detecting gene copy number alterations by Oncomine Comprehensive genomic profiling in a comparative study on FFPE tumor samples Scientific Reports |
| title | Detecting gene copy number alterations by Oncomine Comprehensive genomic profiling in a comparative study on FFPE tumor samples |
| title_full | Detecting gene copy number alterations by Oncomine Comprehensive genomic profiling in a comparative study on FFPE tumor samples |
| title_fullStr | Detecting gene copy number alterations by Oncomine Comprehensive genomic profiling in a comparative study on FFPE tumor samples |
| title_full_unstemmed | Detecting gene copy number alterations by Oncomine Comprehensive genomic profiling in a comparative study on FFPE tumor samples |
| title_short | Detecting gene copy number alterations by Oncomine Comprehensive genomic profiling in a comparative study on FFPE tumor samples |
| title_sort | detecting gene copy number alterations by oncomine comprehensive genomic profiling in a comparative study on ffpe tumor samples |
| url | https://doi.org/10.1038/s41598-025-88494-3 |
| work_keys_str_mv | AT fabiobozzi detectinggenecopynumberalterationsbyoncominecomprehensivegenomicprofilinginacomparativestudyonffpetumorsamples AT elenaconca detectinggenecopynumberalterationsbyoncominecomprehensivegenomicprofilinginacomparativestudyonffpetumorsamples AT marcosilvestri detectinggenecopynumberalterationsbyoncominecomprehensivegenomicprofilinginacomparativestudyonffpetumorsamples AT gianpaolodagrada detectinggenecopynumberalterationsbyoncominecomprehensivegenomicprofilinginacomparativestudyonffpetumorsamples AT aliceardore detectinggenecopynumberalterationsbyoncominecomprehensivegenomicprofilinginacomparativestudyonffpetumorsamples AT donatapenso detectinggenecopynumberalterationsbyoncominecomprehensivegenomicprofilinginacomparativestudyonffpetumorsamples AT danielelorenzini detectinggenecopynumberalterationsbyoncominecomprehensivegenomicprofilinginacomparativestudyonffpetumorsamples AT chiaracostanzavolpi detectinggenecopynumberalterationsbyoncominecomprehensivegenomicprofilinginacomparativestudyonffpetumorsamples AT desireviolatrupia detectinggenecopynumberalterationsbyoncominecomprehensivegenomicprofilinginacomparativestudyonffpetumorsamples AT adelebusico detectinggenecopynumberalterationsbyoncominecomprehensivegenomicprofilinginacomparativestudyonffpetumorsamples AT iolandacapone detectinggenecopynumberalterationsbyoncominecomprehensivegenomicprofilinginacomparativestudyonffpetumorsamples AT federicaperrone detectinggenecopynumberalterationsbyoncominecomprehensivegenomicprofilinginacomparativestudyonffpetumorsamples AT elenatamborini detectinggenecopynumberalterationsbyoncominecomprehensivegenomicprofilinginacomparativestudyonffpetumorsamples AT andreavingiani detectinggenecopynumberalterationsbyoncominecomprehensivegenomicprofilinginacomparativestudyonffpetumorsamples AT lucaagnelli detectinggenecopynumberalterationsbyoncominecomprehensivegenomicprofilinginacomparativestudyonffpetumorsamples AT giancarlopruneri detectinggenecopynumberalterationsbyoncominecomprehensivegenomicprofilinginacomparativestudyonffpetumorsamples |