Abstract

Modification of the Hi-C Technology for Molecular Genetic Analysis of Formalin-Fixed Paraffin-Embedded Sections of Tumor Tissues

Maria M. Gridina^1,2,a*, Yana K. Stepanchuk^1,2, Miroslav A. Nurridinov^1,2, Timofey A. Lagunov^1,2, Nikita Yu. Torgunakov^1,2, Artem A. Shadsky^1,2, Anastasia I. Ryabova³, Nikolay V. Vasiliev³, Sergey V. Vtorushin^3,5, Tatyana S. Gerashchenko³, Evgeny V. Denisov³, Mikhail A. Travin⁴, Maxim A. Korolev⁴, and Veniamin S. Fishman^1,2

¹Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia

²Novosibirsk State University, 630090 Novosibirsk, Russia

³Research Institute of Oncology, Tomsk National Research Medical Center, Russian Academy of Sciences, 634009 Tomsk, Russia

⁴Research Institute of Clinical and Experimental Lymphology, Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 630117 Novosibirsk, Russia

⁵Siberian State Medical University, Ministry of Health of Russia, 634050 Tomsk, Russia

Received September 5, 2023; Revised October 31, 2023; Accepted October 31, 2023
Molecular genetic analysis of tumor tissues is the most important step towards understanding the mechanisms of cancer development; it is also necessary for the choice of targeted therapy. The Hi-C (high-throughput chromatin conformation capture) technology can be used to detect various types of genomic variants, including balanced chromosomal rearrangements, such as inversions and translocations. We propose a modification of the Hi-C method for the analysis of chromatin contacts in formalin-fixed paraffin-embedded (FFPE) sections of tumor tissues. The developed protocol allows to generate high-quality Hi-C data and detect all types of chromosomal rearrangements. We have analyzed various databases to compile a comprehensive list of translocations that hold clinical importance for the targeted therapy selection. The practical value of molecular genetic testing is its ability to influence the treatment strategies and to provide prognostic insights. Detecting specific chromosomal rearrangements can guide the choice of the targeted therapies, which is a critical aspect of personalized medicine in oncology.
KEY WORDS: chromosomal rearrangements, three-dimensional nuclear organization, oncology, FFPE sections
DOI: 10.1134/S0006297924040047
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