Detection of fusion events by RNA sequencing in FFPE versus freshly frozen colorectal cancer tissue samples
Gene fusion events result in chimeric proteins that are frequently found in human cancers. Specific targeted therapies are available for several types of cancer fusions including receptor tyrosine kinase gene moieties. RNA sequencing (RNAseq) can directly be used for detection of gene rearrangements...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2024.1448792/full |
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| author | Maxim Sorokin Maxim Sorokin Maxim Sorokin Maxim Sorokin Vladimir Lyadov Vladimir Lyadov Vladimir Lyadov Maria Suntsova Marat Garipov Anna Semenova Natalia Popova Egor Guguchkin Rustam Heydarov Marianna Zolotovskaia Xiaowen Zhao Qing Yan Ye Wang Evgeny Karpulevich Anton Buzdin Anton Buzdin Anton Buzdin Anton Buzdin |
| author_facet | Maxim Sorokin Maxim Sorokin Maxim Sorokin Maxim Sorokin Vladimir Lyadov Vladimir Lyadov Vladimir Lyadov Maria Suntsova Marat Garipov Anna Semenova Natalia Popova Egor Guguchkin Rustam Heydarov Marianna Zolotovskaia Xiaowen Zhao Qing Yan Ye Wang Evgeny Karpulevich Anton Buzdin Anton Buzdin Anton Buzdin Anton Buzdin |
| author_sort | Maxim Sorokin |
| collection | DOAJ |
| description | Gene fusion events result in chimeric proteins that are frequently found in human cancers. Specific targeted therapies are available for several types of cancer fusions including receptor tyrosine kinase gene moieties. RNA sequencing (RNAseq) can directly be used for detection of gene rearrangements in a single test, along with multiple additional biomarkers. However, tumor biosamples are usually formalin-fixed paraffin-embedded (FFPE) tissue blocks where RNA is heavily degraded, which in theory may result in decreased efficiency of fusion detection. Here, for the first time, we compared the efficacy of gene fusion detection by RNAseq for matched pairs of freshly frozen in RNA stabilizing solution (FF) and FFPE tumor tissue samples obtained from 29 human colorectal cancer patients. We detected no statistically significant difference in the number of chimeric transcripts in FFPE and FF RNAseq profiles. The known fusion KANSL1-ARL17A/B occurred with a high frequency in 69% of the patients. We also detected 93 new fusion genes not mentioned in the literature or listed in the ChimerSeq database. Among them, 11 were found in two or more patients, suggesting their potential role in carcinogenesis. Most of the fusions detected most probably represented read-through, microdeletion or local duplication events. Finally, in one patient, we detected a potentially clinically actionable in-frame fusion of LRRFIP2 and ALK genes not previously described in colorectal cancer with an intact tyrosine kinase domain that can be potentially targeted by ALK inhibitors. |
| format | Article |
| id | doaj-art-43e8a32f012c4960866706fcd6b0519c |
| institution | Kabale University |
| issn | 2296-889X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj-art-43e8a32f012c4960866706fcd6b0519c2025-01-21T09:00:43ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2025-01-011110.3389/fmolb.2024.14487921448792Detection of fusion events by RNA sequencing in FFPE versus freshly frozen colorectal cancer tissue samplesMaxim Sorokin0Maxim Sorokin1Maxim Sorokin2Maxim Sorokin3Vladimir Lyadov4Vladimir Lyadov5Vladimir Lyadov6Maria Suntsova7Marat Garipov8Anna Semenova9Natalia Popova10Egor Guguchkin11Rustam Heydarov12Marianna Zolotovskaia13Xiaowen Zhao14Qing Yan15Ye Wang16Evgeny Karpulevich17Anton Buzdin18Anton Buzdin19Anton Buzdin20Anton Buzdin21OmicsWay Corp., Covina, CA, United StatesPathoBiology Group, European Organization for Research and Treatment of Cancer (EORTC), Brussels, BelgiumInstitute of Personalized Oncology, I.M. Sechenov First Moscow State Medical University, Moscow, RussiaMoscow Center for Advanced Studies, Moscow, RussiaMoscow State Budgetary Healthcare Institution “Moscow City Oncological Hospital N1, Moscow Healthcare Department”, Moscow, RussiaFederal State Budgetary Educational Institution of Further Professional Education “Russian Medical Academy of Continuous Professional Education” of the Ministry of Healthcare of the Russian Federation, Moscow, RussiaNovokuznetsk State Institute for Advanced Training of Physicians – Branch of RMACPE, Novokuznetsk, RussiaInstitute of Personalized Oncology, I.M. Sechenov First Moscow State Medical University, Moscow, RussiaMoscow State Budgetary Healthcare Institution “Moscow City Oncological Hospital N1, Moscow Healthcare Department”, Moscow, RussiaMoscow State Budgetary Healthcare Institution “Moscow City Oncological Hospital N1, Moscow Healthcare Department”, Moscow, RussiaMoscow State Budgetary Healthcare Institution “Moscow City Oncological Hospital N1, Moscow Healthcare Department”, Moscow, RussiaInstitute for System Programming of RAS, Moscow, RussiaInstitute of Personalized Oncology, I.M. Sechenov First Moscow State Medical University, Moscow, RussiaMoscow Center for Advanced Studies, Moscow, RussiaCore lab, Qingdao Central Hospital, University of Health and Rehabilitation Sciences, Qingdao, ChinaCore lab, Qingdao Central Hospital, University of Health and Rehabilitation Sciences, Qingdao, ChinaCore lab, Qingdao Central Hospital, University of Health and Rehabilitation Sciences, Qingdao, ChinaInstitute for System Programming of RAS, Moscow, RussiaPathoBiology Group, European Organization for Research and Treatment of Cancer (EORTC), Brussels, BelgiumMoscow Center for Advanced Studies, Moscow, Russia0Group for Genomic Regulation of Cell Signaling Systems, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia1World-Class Research Center “Digital Biodesign and Personalized Healthcare”, Sechenov First Moscow State Medical University, Moscow, RussiaGene fusion events result in chimeric proteins that are frequently found in human cancers. Specific targeted therapies are available for several types of cancer fusions including receptor tyrosine kinase gene moieties. RNA sequencing (RNAseq) can directly be used for detection of gene rearrangements in a single test, along with multiple additional biomarkers. However, tumor biosamples are usually formalin-fixed paraffin-embedded (FFPE) tissue blocks where RNA is heavily degraded, which in theory may result in decreased efficiency of fusion detection. Here, for the first time, we compared the efficacy of gene fusion detection by RNAseq for matched pairs of freshly frozen in RNA stabilizing solution (FF) and FFPE tumor tissue samples obtained from 29 human colorectal cancer patients. We detected no statistically significant difference in the number of chimeric transcripts in FFPE and FF RNAseq profiles. The known fusion KANSL1-ARL17A/B occurred with a high frequency in 69% of the patients. We also detected 93 new fusion genes not mentioned in the literature or listed in the ChimerSeq database. Among them, 11 were found in two or more patients, suggesting their potential role in carcinogenesis. Most of the fusions detected most probably represented read-through, microdeletion or local duplication events. Finally, in one patient, we detected a potentially clinically actionable in-frame fusion of LRRFIP2 and ALK genes not previously described in colorectal cancer with an intact tyrosine kinase domain that can be potentially targeted by ALK inhibitors.https://www.frontiersin.org/articles/10.3389/fmolb.2024.1448792/fullcolorectal cancerformalin-fixed paraffin-embedded tumor tissue samplesFFPERNA sequencingRNAseqnew cancer fusion genes |
| spellingShingle | Maxim Sorokin Maxim Sorokin Maxim Sorokin Maxim Sorokin Vladimir Lyadov Vladimir Lyadov Vladimir Lyadov Maria Suntsova Marat Garipov Anna Semenova Natalia Popova Egor Guguchkin Rustam Heydarov Marianna Zolotovskaia Xiaowen Zhao Qing Yan Ye Wang Evgeny Karpulevich Anton Buzdin Anton Buzdin Anton Buzdin Anton Buzdin Detection of fusion events by RNA sequencing in FFPE versus freshly frozen colorectal cancer tissue samples Frontiers in Molecular Biosciences colorectal cancer formalin-fixed paraffin-embedded tumor tissue samples FFPE RNA sequencing RNAseq new cancer fusion genes |
| title | Detection of fusion events by RNA sequencing in FFPE versus freshly frozen colorectal cancer tissue samples |
| title_full | Detection of fusion events by RNA sequencing in FFPE versus freshly frozen colorectal cancer tissue samples |
| title_fullStr | Detection of fusion events by RNA sequencing in FFPE versus freshly frozen colorectal cancer tissue samples |
| title_full_unstemmed | Detection of fusion events by RNA sequencing in FFPE versus freshly frozen colorectal cancer tissue samples |
| title_short | Detection of fusion events by RNA sequencing in FFPE versus freshly frozen colorectal cancer tissue samples |
| title_sort | detection of fusion events by rna sequencing in ffpe versus freshly frozen colorectal cancer tissue samples |
| topic | colorectal cancer formalin-fixed paraffin-embedded tumor tissue samples FFPE RNA sequencing RNAseq new cancer fusion genes |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2024.1448792/full |
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