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Estimating molecular variability of patient-derived xenografts of esophageal cancerстатья
Статья опубликована в высокорейтинговом журнале
Статья опубликована в журнале из списка Web of Science и/или Scopus- Авторы: Protasova Tatiana P., Timoshkina Natalya N., Kolesnikov Evgeniy N., Averkin Mikhail A., Gaziev Umar Muhmadovich, Kit Sergei, Anisimov Aleksandr E., Goncharova Anna S., Kutilin Denis S., Volkova A.V., Mindar M.V., Tkachev Sergey Yu, Zaikina Ekaterina V., Khodakova D.V., Lukbanova Ekaterina A., Maksimov Aleksey Yu, Vladimirova Liubov Yu, Kit Oleg I.
- Журнал: Journal of Clinical Oncology
- Том: 38
- Номер: 15_suppl
- Год издания: 2020
- Издательство: American Society of Clinical Oncology
- Местоположение издательства: United States
- Первая страница: e13649
- Последняя страница: e13649
- DOI: 10.1200/jco.2020.38.15_suppl.e13649
- Аннотация: Background: The survival of patients with esophageal squamous cell carcinoma depends not only on clinical signs (TNM, tumor site), but also on the molecular genetic subtype of the tumor. Identification of the molecular genetic subtype and the presence/absence of clinically significant mutations is an important step towards finding new effective drugs and choosing the most appropriate therapeutic strategies. A patient-derived xenograft (PDX) model is a valuable resource to solving the problem, provided that the model accurately reproduces the basic clinical and molecular genetic characteristics of a human tumor. Our purpose was to create a PDX model of a human tumor and to study 7 polymorphisms of the xenograft tissue and tissues of a donor tumor. Methods: PDX models of esophageal cancer were produced by transplanting a tumor fragment from a patient with esophageal squamous cell carcinoma to the BALB/c Nude athymic mice (n = 10 for one PDX generation). 5 PDX were generated. 7 polymorphisms (NFE2L2 (c.85G > A), NOTCH1 (c.1379C > T), NOTCH1 (c.1451G > T), ZNF750 (c.414C > A), ZNF750 (c.1621G > A), SMARCA4 (c.2272C > T), KMT2D (c.15508C > T)) were determined by the HRM analysis in tissues of each PDX generation and in the donor tumor. Results: All examined samples demonstrated the absence of ZNF750 (c.1621G > A) and NOTCH1 (c.1379C > T) polymorphisms and the presence of ZNF750 (c.414C > A), SMARCA4 (c.2272C > T) and KMT2D (c.15508C > T) polymorphisms. Polymorphisms in the NFE2L2 (c.85G > A) gene and in the NOTCH1 (c.1451G > T) gene were found in the F3, F4 and F5 PDX generations, but were absent in the donor tumor and the F1 and F2 generations. Conclusions: Molecular and genetic characteristics of the donor tumor change through several PDX generations. Early PDX generations are recommended for the studies as they better reproduce molecular and genetic characteristics of the original tumors.
- Добавил в систему: Владимирова Любовь Юрьевна