Gene staging: rare head and neck tumors will be easier to detect
Scientists have identified about 50 previously unknown mutations in genes that could potentially be associated with the development of paragangliomas of the head and neck - tumors affecting the neuroendocrine system. The data obtained will be useful in the diagnosis and development of new methods of treatment of these neoplasms. Based on this information, scientists aim to develop molecular targeting therapy for these tumors - an approach that uses a drug that specifically targets the affected cells.
Head and neck tumors
Scientists from the V.A. Engelg Institute of Molecular Biology in Moscow, Russia. V.A. Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences and colleagues conducted a genetic analysis of head and neck paragangliomas to identify mutations specific to them.
Evos microscope work: scientist shows primary paraganglioma cell lines stained for key markers
The authors examined 152 tumor samples from 140 patients collected in collaboration with the staff of the Vishnevsky National Medical Research Center for Surgery. A.V. Vishnevsky National Medical Research Center for Surgery of the Ministry of Health. The biologists extracted DNA from the tumor cells and decoded its sequence. Then, using bioinformatics programs, they identified mutant genes, determined their functions and assessed their possible participation in the transformation of a cell from healthy to malignant. In 30% of the tumors studied, the authors found 53 potentially harmful mutations in 36 different genes.
- The association of most of the detected mutations with head and neck paragangliomas was not previously known. The identified genetic variants may have negative effects on protein structure and function. The predicted harmful effects of these mutations suggest that they may be involved in oncogenesis," Anastasia Snezhkina, Ph.D., a leading researcher at the Institute of Molecular Biology, told Izvestia.
Paragangliomas of the head and neck are a rare type of tumors arising in neuroendocrine tissue. Such neoplasms are diagnosed annually in about one person out of 30-100 thousand people. They are usually removed surgically, but such operations are quite risky. This is due to the fact that paragangliomas of the head and neck are often located near large blood vessels and cranial nerves, which can be accidentally damaged. Scientists are therefore seeking to develop molecular targeted therapies for these tumors, an approach that uses a drug that targets strictly the cells of the neoplasm. To find such a drug, it is necessary to identify specific features of cancer cells - biomarkers. These can be mutations in genes. A number of mutations characteristic of paragangliomas of the head and neck are already known, but for accurate diagnosis and personalized therapy, their list should be expanded.
Gene mutations in cancerous tumors
According to the authors, most mutant genes are involved in the cell's metabolic and energy supply processes, as well as in known signaling pathways often associated with cancer.
- Our study has allowed us to identify genetic abnormalities occurring in head and neck paragangliomas, which is important for the development of new methods of diagnosis and treatment of these tumors. In the future, we plan to experimentally test how the mutations we have identified affect cellular processes and disease progression," said Anastasia Snezhkina.
Creation of PCR mixture
Scientists decoded mutations in already formed tumors, that is, they focused on the study of so-called driver mutations that give cancer cells advantages and contribute to their malignant nature, Albert Rizvanov, head of the Center of Excellence "Personalized Medicine" of Kazan (Volga Region) Federal University, corresponding member of the Academy of Sciences of the Republic of Tatarstan, told Izvestia. According to him, it is they who serve as targets for target therapy.
- For example, for the search for lung cancer inhibitors, finding new mutations that can serve as targets for targeted therapy is an extremely important task. Knowing them will make it easier for doctors to select drugs. At the same time, it would be interesting to see the contribution of inherited mutations, so-called terminal mutations, in the development of rare tumors," he said.
Itis one thing to identify a mutation, but another thing to prove that it is the cause of the disease, and this is quite difficult, said Izvestia senior researcher at the Institute of Immunology and Physiology of the Ural Branch of the Russian Academy of Sciences Mikhail Bolkov.
- For this purpose, bioinformatic elements are used. Theoretically, the identified mutations can then be targeted. But now this work is at the very beginning, scientists have removed the top layer to see what's underneath," the expert said.
The PCR mixture is dispersed into tubes using a pipetting device
The results of the study, supported by a grant from the Russian Science Foundation, were published in the journal International Journal of Molecular Sciences. Employees of Ulyanovsk State University and Ulyanovsk Regional Clinical Oncologic Dispensary also took part in the work.
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