Molecular genetic sequencing of neuroendocrine tumors of the gastrointestinal tract.

Abstract

651 Background: The objective of this work was to evaluate the molecular and genetic features of the NET gastrointestinal tract. Genomic sequencing of 30 tumor samples of the latest generation was carried out and the data obtained were evaluated. Methods: In total, 30 tumor blocks of patients with gastrointestinal NET were tested by the new generation sequencing (NGS) method. The following genes were analyzed: ATM, ATR, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CDK12, CHEK1, CHEK2, EPCAM, FANCL, MLH1, MSH2, NBN, NF1, PALB2, PMS2, RAD51B, RAD51C, RAD51D, RAD54L, STK11, TP53, POLE, KRAS, NRAS, BRAF, EGFR, ERBB2, PIK3CA, MET ex14, BAT25, BAT26, NR21, NR24, MONO27, KIT, PDGFRA, Pi3Ca. Preparation of libraries for sequencing was carried out using NimblGen SepCapEZ Choice. Sequencing was performed on the Illumina MiSeq device. Results: In the study cohort of patients whose tumor blocks were sent for examination by the NGS method, there were more women – 19 (63.3%) than men – 11 (36.7%). When analyzing the age of patients, it should be noted that among all age groups, elderly patients predominated (60-74 years according to the WHO classification, 2016) – 12 (40%). In the majority of patients – 10 (33.3%) – the primary tumor focus was localized in the pancreas, in 6 (20%) patients it was primarily affected stomach, 7 (23.3%) – small intestine. Other parts of the gastrointestinal tract were affected much less frequently: the colon – in 1 (3.3%) patients. According to the division according to the degree of differentiation of gastrointestinal NET10 tumors had a degree of differentiation G1 (33.3%), 16 -G3 (54.3%), 4– G3 (13.3%). In the tumor sample of a patient with gastric NET G1 (Ki 67 = 2%), POLE mutations were found: c.2276G > A, p.R759H and CHEK2: c.470T > C, p.I157T. Also, mutations MLH1: c.199G > A, p.G67R BRCA1: c.1881 were found in the tumor sample of another patient with gastric NET G2 (Ki 67 = 7%). Conclusions: To improve the survival rates of patients, it is worth paying special attention to the molecular genetic study of the NET gastrointestinal tract. It is molecular genetic profiling that can become the basis for building more individualized algorithms for treating patients. The results of this study allow us to count on the fact that when conducting a study on a larger cohort of patients with gastrointestinal NET, it is possible to obtain results that will expand our knowledge of this nosology and allow us to supplement the already available information about prognosis factors and predictors of response to treatment.