A.A. Androsova1,2, R.V. Orlova1,2, M.G. Gordiev4, A.K. Ivanova2, N.P. Belyak1,2, S.I. Kutukova2,3
1Saint Petersburg State University, Saint Petersburg
2City Clinical Oncology Center, Saint Petersburg
3Pavlov University, Saint Petersburg
4Medical and Diagnostic Center of the International Institute of Biological Systems named after Sergey Berezin, Saint Petersburg
Androsova Aleхandra V. ― postgraduate student of the Saint Petersburg State University, oncologist of Cancer Drug Therapy (Chemotherapeutic) Department №10 of the City Clinical Oncology Center
56 Veteranov Ave., Saint Petersburg, 198255, Russian Federation, e-mail: email@example.com, ORCID ID: 0000-0001-7111-1507
Abstract. Neuroendocrine tumors (NEO) are a heterogeneous group of neoplasms. Over the past 30 years, there has been an increase in the number of NEO diseases by 720%. The expansion of knowledge about the molecular and genetic nature of the NEO of the gastrointestinal tract (GIT) is currently an important task, the solution of which will improve the algorithms for the treatment of the disease.
The aim of the study is to study the frequency of pathogenic somatic mutations in the tumor material of patients diagnosed with gastrointestinal NEO.
The article analyzes the works of Katerina Zakka, Scarpa A., Faviana, P. (et al.), Lin L.-Y. (et al.); the results of a study based on complete genomic sequencing are presented; the hypothesis is formulated that a better understanding of the carcinogenesis of NEO will lead to the discovery of prognostic biomarkers that can help individualize the treatment of patients with NEO Gastrointestinal tract.
As a result of our own study of biomarkers, pathogenic mutations were detected in 9 out of 40 analyzed tumor samples (22,5%). The most frequent mutations were BRCA 1 (3/7,5%) and BRCA 2 (3/7,5%). POLE mutation was found in 2 tumor samples (2/5%). Also in the studied samples there were such mutations as PTEN (2,5%/1) (in combination with BRCA 1), PIK3CA (2,5%/1), RB1 (2,5%/1) (in combination with BRCA 2), CHEK2 (2,5%/1) (in combination with POLE), MLH1(2,5%/1) (in combination with BRCA 1), t790m (2,5%/1) (in combination with BRCA 1).
Taking into account the heterogeneity of clinical and morphological forms of NEO and different approaches to treatment, depending on the morphological form, proliferation index, as well as the complexity of differential diagnosis, special attention is required to this nosology, since the right treatment affects survival rates. To improve these indicators, it is worth paying special attention to the molecular genetic study of the NEO gastrointestinal tract. It can become a support for building individualized algorithms for the treatment of patients. It is worth noting that according to the results of our study, 77,5% of the NEO gastrointestinal tract is characterized by the absence of pathogenic somatic mutations («wild type»). It is especially worth noting that the most frequent mutations were BRCA 1 (3/7,5%) and BRCA 2 (3/7,5%). The results of such studies can subsequently expand our knowledge of this nosology and will allow us to supplement information about prognostic factors and predictors of response to treatment.
Key words: neuroendocrine tumors, pathogenic somatic mutations, gastrointestinal tract, pancreas, genomic sequencing.