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DNA repair pathway activation features in follicular and papillary thyroidtumors, interrogated using 95 experimental RNA sequencing profilesстатья Электронная публикация
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 4 июня 2021 г.
- Авторы: Vladimirova Uliana, Rumiantsev Pavel, Zolotovskaia Marianna, Albert Eugene, Abrosimov Aleksander, Slashchuk Konstantin, Nikiforovich Petr, Chukhacheva Olga, Gaifullin Nurshat, Suntsova Maria, Zakharova Galina, Glusker Alexander, Nikitin Daniil, Garazha Andrew, Li Xinmin, Kamashev Dmitriy, Drobyshev Alexei, Kochergina-Nikitskay Irina, Sorokin Maxim, Buzdin Anton
- Журнал: Heliyon
- Том: 7
- Номер: 3
- Год издания: 2021
- Издательство: Elsevier Science Publishing Company, Inc.
- Местоположение издательства: Нидерланды
- Первая страница: e06408
- DOI: 10.1016/j.heliyon.2021.e06408
- Аннотация: DNA repair can prevent mutations and cancer development, but it can also restore damaged tumor cells after chemo and radiation therapy. We performed RNA sequencing on 95 human pathological thyroid biosamples including 17 follicular adenomas, 23 follicular cancers, 3 medullar cancers, 51 papillary cancers and 1 poorly differentiated cancer. The gene expression profiles are annotated here with the clinical and histological diagnoses and, for papillary cancers, with BRAF gene V600E mutation status. DNA repair molecular pathway analysis showed strongly upregulated pathway activation levels for most of the differential pathways in the papillary cancer and moderately upregulated pattern in the follicular cancer, when compared to the follicular adenomas. This was observed for the BRCA1, ATM, p53, excision repair, and mismatch repair pathways. This finding was validated using independent thyroid tumor expression dataset PRJEB11591. We also analyzed gene expression patterns linked with the radioiodine resistant thyroid tumors (n¼13) and identified 871 differential genes that according to Gene Ontology analysis formed two functional groups: (i) response to topologically incorrect protein and (ii) aldo-keto reductase (NADP) activity. We also found RNA sequencing reads for two hybrid transcripts: one in-frame fusion for well-known NCOA4-RET translocation, and another frame shift fusion of ALK oncogene with anew partnerARHGAP12. The latter could probably support increased expression of truncated ALK downstream from 4thexon out of 28. Both fusions were found in papillary thyroid cancers of follicular histologic subtype with node metastases, one of them (NCOA4-RET) for the radioactive iodine resistant tumor. The differences in DNA repair activation patterns may help to improve therapy of different thyroid cancer types under investigation and the data communicated may serve for finding additional markers of radioiodine resistance.
- Добавил в систему: Гайфуллин Нуршат Минуллаевич