Identification of large deletions in the APC gene in Russian patients with familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) is a hereditary syndrome characterized by the presence of multiple adenomatous polyps in the colon. The main cause of the disease is a germline mutation in the APC gene. Here we report 4 unrelated FAP patients with different large deletions in the APC gene detected by Multiplex Ligation-dependent Probe Amplification (MLPA) method: deletion of exons 7-15, deletion of promoters B, A, and 5'-UTR region and deletion of promoter B (in 2 patients). The deletion of promoters B, A, and 5'-UTR was not described in the literature earlier, so we report it for the first time. In 2 families with promoter B deletion, we could identify the tendency for decreasing the age of disease manifestation in each next generation, in contrast to the previous one. The incidence of large deletions in APC among Russian patients with FAP reached 4.8% and our finding suggests the need to study this gene by MLPA in "no mutation patients" after Sanger's sequencing.

[Factors affecting the survival of patients with peritoneal carcinomatosis of colorectal origin]. / Faktory prognoza vyzhivaemosti bol'nykh, operirovannykh po povodu peritoneal'nogo kartsinomatoza pri rake tolstoi kishki.

One of the main problems in the treatment of peritoneal carcinomatosis (PC) in colorectal cancer (CRC) is the adequate selection of patients for cytoreductive surgery (CS) and hyperthermic intraperitoneal chemotherapy (HIPEC). AIM: To determine the predictive factors of overall (OS) and disease-free survival (DFS) in CRC patients with PC after CS with HIPEC. MATERIAL AND METHODS: From 2010 to 2018 years 102 patients with CRC and PC were included in the study. The cytoreduction was complete (CC0, according to Sugabaker scale) in 96 (94.2%) cases. The age median of patients was 65 years. There were 63 (62%) women. In 81 (79%) patients, the PC was synchronous. The median level of CEA was 8.5 ng/ml. The median peritoneal carcinomatous index (PCI) was 3 (1-23). RESULTS: The median of follow-up was 18 (11; 33) months. The median of DFS and OS were 13 (9;31) and 32 (17; n/d) months, respectively. Multifactorial Cox-regression analysis showed the localization of the primary tumor in the right colon (OR=1.66; 95% CI 1.1-2.5; p=0.013) and the level of the PCI (OR = 1.08; 95% CI 1.024-1.15; p=0.008) were independent negative factors of OS. CONCLUSION: The CS and HIPEC in patients with CRC with PC allowes to achieve five-year survival in a part of patients, especially with low PCI. Identifying adverse prognostic factors preoperatively can help in selecting patients for CS in the future.

[Pilot clinical and genetic study of Russian patients with Peutz-Jeghers syndrome].

Peutz-Jeghers syndrome is a rare hereditary syndrome characterized by presence of hamartoma polyps in intestinal tract and usually by mucocutaneous pigmentation. Clinical-genetic characteristics of Russian patients with Peutz-Jeghers syndrome were studied for the first time. Four germline mutations in STK11gene were found in probands from six families and three of them had not been described previously. Clinical pattern of disease in Russian patients included: frequent polyposis of colon and stomach (62,5% and 75%, respectively) along with small bowel; frequent presence of malignant tumors (62,5%). These clinical aspects can help physicians to find out Peutz-Jeghers syndrome. Molecular-genetic testing of individuals should be recommended.

The analysis of microRNAs miR-200C and miR-145 expression in colorectal cancer of different molecular subtypes.

The expression levels of microRNAs miR-200c and miR-145 in two groups of colorectal cancer differing by the presence/absence of epithelial-mesenchymal transition (EMF) were studied. In the EMF-positive cancer, the level of miR-145 is increased, whereas the level of miR-200c is reduced. The reverse situation is observed in the EMI-negative cancer. MiR-145 can serve as a marker of the mesenchymal subtype of cancer. Gene expression profiles and microRNAs allow prognostically unfavorable tumors of the mesenchymal subtype to be distinguished.

Epithelial-mesenchymal transition and somatic alteration in colorectal cancer with and without peritoneal carcinomatosis.

Colorectal cancer is highly metastatic even when the tumors are small. To disseminate, cells use a complex and multistage process known as the epithelial-mesenchymal transition, in which epithelial phenotype is transformed into mesenchymal phenotype. The objective of this study is to describe the epithelial-mesenchymal transition in terms of gene expression profile and somatic alterations in samples of colorectal cancer with or without peritoneal carcinomatosis. We analyzed samples taken from 38 patients with colorectal cancer (stages II-IV) and samples from 20 patients with colorectal cancer complicated by peritoneal carcinomatosis. The expression of ZEB1, ZEB2, CDH1, VIM, and SNAI1 was analyzed by real-time PCR. KRAS/BRAF mutations were mapped using sequencing. Microsatellite instability was evaluated by fragment analysis. Epithelial-mesenchymal transition was detected in 6 out of 38 samples of colorectal cancer (stages II-IV), 7 out of 20 tumors from patients with peritoneal carcinomatosis, and 19 out of 20 samples taken from carcinomatous nodules. Tumors of the mesenchymal subtype displayed high frequency of somatic mutations, microsatellite stability, and low degree of differentiation. The identification of epithelial-mesenchymal transition may be used as a marker of high metastatic potential, which is particularly relevant at early stages of tumor growth.

[Molecular genetics study of hereditary predisposition to diffuse gastric cancer in Russian patients].

About 3% of cases of gastric cancer (GC) cases are due to hereditary predisposition. Molecular causes of inherited predisposition to diffuse GC among Russian patients have not been studied. In the present work there was performed the molecular genetics study in 9 probands with signet-ring cell GC. Search of hereditary mutations was conducted in a suppressor gene of diffuse GC - the gene CDH1. We have discovered a new hereditary mutation (c.1005delA) and one rare variant (s.2253C> T). Frequency of hereditary mutations in sample of patients Russian was 1/9 (11,1%).