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.
The 5382insC mutation predominated (94%) in the spectrum of detected mutations of BRCA1 gene. High incidence of this mutation in familial breast cancer detected for the first time attested to origination of 5382insC mutation from the European part of Russia. The percentage of families with mutations in BRCA1 gene and familial predisposition to ovarian cancer was significantly higher than in hereditary predisposition to breast cancer (p<0.007). These data suggest that clinical manifestation of the mutation depends on genotypical factors other than the position of this mutation in BRCA1 gene. The results prompt screening for hereditary predisposition to these diseases.
The incidence of mutations in the BRCA1 and BRCA2 genes in the studied sampling of 74 patients with ovarian cancer was 19%. The incidence of mutations in the Russian sampling of patients, formed without consideration for the family history, is one of the highest in European countries. Retrospective analysis showed that 9% patients carrying mutation had no family history of ovarian or breast cancer. The majority of mutations (86%) were detected in BRCA1 gene, where 5382insC mutation predominated (58%). These data suggest the possibility and advisability of screening for mutations in the BRCA1/2 genes in patients with ovarian cancer, particularly because this population includes patients without family history of ovarian and/or breast cancer.
The most serious complication of breast cancer (BC), which affects life expectancy, is metastasis of the tumor. Metastasis is the cause of more than 80% of all breast cancer deaths. After surgical treatment and the use of adjuvant therapy, metastases occur in 8% 15% of cases. This indicates the need to develop markers for the prognosis of metastasis and clarify its mechanisms for the creation of anti-metastatic therapeutic agents. In this paper, we studied the association of LOX and uPAR gene expression with breast cancer metastasis in the lymph nodes.
Gene expression was measured using real-time PCR in 40 paired samples (tumor-normal tissues). As a result of processing the measurements, the values of gene expression levels in the tumor tissue relative to normal were obtained.
It is shown that the LOX gene is expressed in the tumor both lower and higher relative to the norm, and uPAR is expressed in most cases higher. In metastatic tumors, the frequency of expression increases above the norm for both LOX and uPAR genes. The association of expression of these genes with lymphatic metastasis was found: p = 0.01 and p = 0.02, for the LOX and uPAR genes, respectively. The relative risk (RR) was for the LOX gene RR = 1.9, 95% CI 1.2 3, p = 0.005, for uPAR RR = 3.6, 95% CI 1.2 10.9, p = 0.03.
Thus, the data obtained contribute to understanding the mechanisms of metastasis and provide the basis for the development of new biomarkers. The LOX and uPAR genes may be candidates for predictive markers of breast cancer metastasis risk.
Gastric cancer is one of the most common malignancies worldwide. Approximately 10 % of patients with gastric cancer are characterized by accumulation of gastric cancer cases in their family. The hereditary forms of gastric cancer account for 1–3 % of all gastric cancer cases. Hereditary diffuse GC syndrome is caused by germline mutations in CDH1 gene and determines a high risk of developing diffuse GC and lobular breast cancer. In this article, we present a clinical case of a 41-year-old patient with diffuse gastric cancer, who was found to be a carrier of novel germline mutation in the CDH1 gene. Next-generation sequencing (NGS) has facilitated an identification of CDH1 c.1596G>A genetic variant, thus enabling an accurate clinical diagnosis hereditary diffuse gastric cancer.
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