Your browser doesn't support javascript.
loading
Experimentally Deduced Criteria for Detection of Clinically Relevant Fusion 3' Oncogenes from FFPE Bulk RNA Sequencing Data.
Rabushko, Elizaveta; Sorokin, Maxim; Suntsova, Maria; Seryakov, Alexander P; Kuzmin, Denis V; Poddubskaya, Elena; Buzdin, Anton A.
  • Rabushko E; Laboratory for Clinical and Genomic Bioinformatics, Institute of Personalized Oncology, I.M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia.
  • Sorokin M; Department of Biological and Medical Physics, Moscow Institute of Physics and Technology, 141701 Dolgoprudny, Russia.
  • Suntsova M; Laboratory for Clinical and Genomic Bioinformatics, Institute of Personalized Oncology, I.M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia.
  • Seryakov AP; Department of Biological and Medical Physics, Moscow Institute of Physics and Technology, 141701 Dolgoprudny, Russia.
  • Kuzmin DV; OmicsWay Corp., 340 S Lemon Ave, 6040, Walnut, CA 91789, USA.
  • Poddubskaya E; Laboratory for Clinical and Genomic Bioinformatics, Institute of Personalized Oncology, I.M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia.
  • Buzdin AA; Department of Biological and Medical Physics, Moscow Institute of Physics and Technology, 141701 Dolgoprudny, Russia.
Biomedicines ; 10(8)2022 Aug 02.
Article en En | MEDLINE | ID: mdl-36009413
Drugs targeting receptor tyrosine kinase (RTK) oncogenic fusion proteins demonstrate impressive anti-cancer activities. The fusion presence in the cancer is the respective drug prescription biomarker, but their identification is challenging as both the breakpoint and the exact fusion partners are unknown. RNAseq offers the advantage of finding both fusion parts by screening sequencing reads. Paraffin (FFPE) tissue blocks are the most common way of storing cancer biomaterials in biobanks. However, finding RTK fusions in FFPE samples is challenging as RNA fragments are short and their artifact ligation may appear in sequencing libraries. Here, we annotated RNAseq reads of 764 experimental FFPE solid cancer samples, 96 leukemia samples, and 2 cell lines, and identified 36 putative clinically relevant RTK fusions with junctions corresponding to exon borders of the fusion partners. Where possible, putative fusions were validated by RT-PCR (confirmed for 10/25 fusions tested). For the confirmed 3'RTK fusions, we observed the following distinguishing features. Both moieties were in-frame, and the tyrosine kinase domain was preserved. RTK exon coverage by RNAseq reads upstream of the junction site were lower than downstream. Finally, most of the true fusions were present by more than one RNAseq read. This provides the basis for automatic annotation of 3'RTK fusions using FFPE RNAseq profiles.
Palabras clave

Texto completo: 1 Banco de datos: MEDLINE Tipo de estudio: Diagnostic_studies / Prognostic_studies Idioma: En Año: 2022 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Tipo de estudio: Diagnostic_studies / Prognostic_studies Idioma: En Año: 2022 Tipo del documento: Article