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ORIGINAL RESEARCH article

Front. Mol. Biosci.
Sec. Molecular Diagnostics and Therapeutics
Volume 11 - 2024 | doi: 10.3389/fmolb.2024.1448792
This article is part of the Research Topic Experimental and Computational Methods in the Development of Diagnostics and Therapeutics for Colon Cancer View all 7 articles

Detection of fusion events by RNA sequencing in FFPE versus freshly frozen colorectal cancer tissue samples

Provisionally accepted
Maxim Sorokin Maxim Sorokin 1*Vladimir Lyadov Vladimir Lyadov 2Maria Suntsova Maria Suntsova 1Marat Garipov Marat Garipov 2*Anna Semenova Anna Semenova 2*Natalia Popova Natalia Popova 2*Egor Guguchkin Egor Guguchkin 3*Rustam Heydarov Rustam Heydarov 1Marianna Arsenovna Zolotovskaia Marianna Arsenovna Zolotovskaia 4Xiaowen Zhao Xiaowen Zhao 5*Qing Yan Qing Yan 5*Ye Wang Ye Wang 5*Evgeny A Karpulevich Evgeny A Karpulevich 3Anton A. Buzdin Anton A. Buzdin 1
  • 1 I.M. Sechenov First Moscow State Medical University, Moscow, Russia
  • 2 Moscow City Clinical Oncological Dispensary №1, Moscow, Moscow Oblast, Russia
  • 3 Institute for System Programming (RAS), Moscow, Moscow Oblast, Russia
  • 4 Moscow Center for Advanced Studies, Moscow, Moscow Oblast, Russia
  • 5 Qingdao Central Hospital, Qingdao, Shandong Province, China

The final, formatted version of the article will be published soon.

    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 formalinfixed 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.

    Keywords: colorectal cancer, Formalin-fixed paraffin-embedded tumor tissue samples, FFPE, RNA sequencing, RNAseq, New cancer fusion genes, Chimeric transcripts, Detection of gene rearrangements

    Received: 13 Jun 2024; Accepted: 20 Dec 2024.

    Copyright: © 2024 Sorokin, Lyadov, Suntsova, Garipov, Semenova, Popova, Guguchkin, Heydarov, Zolotovskaia, Zhao, Yan, Wang, Karpulevich and Buzdin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Maxim Sorokin, I.M. Sechenov First Moscow State Medical University, Moscow, Russia
    Marat Garipov, Moscow City Clinical Oncological Dispensary №1, Moscow, Moscow Oblast, Russia
    Anna Semenova, Moscow City Clinical Oncological Dispensary №1, Moscow, Moscow Oblast, Russia
    Natalia Popova, Moscow City Clinical Oncological Dispensary №1, Moscow, Moscow Oblast, Russia
    Egor Guguchkin, Institute for System Programming (RAS), Moscow, Moscow Oblast, Russia
    Xiaowen Zhao, Qingdao Central Hospital, Qingdao, 266000, Shandong Province, China
    Qing Yan, Qingdao Central Hospital, Qingdao, 266000, Shandong Province, China
    Ye Wang, Qingdao Central Hospital, Qingdao, 266000, Shandong Province, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.