Введение. На сегодняшний день данные иммунофенотипирования используются для стратификации пациентов в рамках крупных многоцентровых исследований по терапии острого лимфобластного лейкоза (ОЛЛ).
Purpose: The epidermal growth factor receptor (EGFR) is overexpressed in several tumor types, and its expression is influenced by the length of a 5 ¶-end microsatellite repeat (CA) n : the longer the repeat, the lower the expression. Dinucleotide repeats accumulate insertion/deletion types of mutations in tumors with microsatellite instability. We designed this study to estimate the occurrence of these mutations in EGFR(CA) n and their relevance in carcinogenesis of microsatellite instability^positive colon and gastric tumors. Experimental Design: We analyzed the frequency of EGFR(CA) n mutations in vivo in 55 colorectal and 14 gastric microsatellite instability^positive cancers, and in vitro in single-cell clone cultures of microsatellite instability^positive colon tumor cell line LS174. Single-cell clone cultures with different repeat lengths were analyzed by fluorescent-activated cell sorter for EGFR cell-surface expression. A correlation analysis was done between EGFR(CA) n mutations and mutations in KRAS, BRAF, and p53. Results: Unlike single-cell clone cultures, which exhibited higher rate of deletions compared with insertions, most of EGFR(CA) n mutations in colon and gastric tumors were insertions. Longer EGFR(CA) n correlated with lower EGFR cell-surface expression in single-cell clone cultures. In colon cancers, the elongation of the repeat was associated negatively with mutations in KRAS and BRAF, but not in p53. Conclusions:The EGFR(CA) n elongation observed in tumors cannot be explained by an intrinsic property of this repeat favoring insertions versus deletions. Instead, a selection for repeat elongation occurs in microsatellite instability^positive tumors, leading to EGFR down-regulation. These findings suggest that in microsatellite instability^positive tumors current therapies targeting EGFR overexpression may have either no effect or an opposite to the expected effect.
Biobanks are the platform for innovative biomedical research in the field of translational and personalized medicine. The important aspect for conducting large-scale research in the field of genomics, transcriptomics, proteomics is the availability of a sample information of the documented high-resolution samples. The biobanks solve the problem of forming groups of patients with different nosology within the population of interest and provide clinical and laboratory information on each sample. The aim of this article is to describe the Biobank processes of the National Medical Research Centre for Oncology within the framework of existing projects and build up collections. The review discusses the main stages of the systematized biobank process, describes the methods of sample preparation of different types of biological material, and also provides statistics of the build up collections. To this date, the predominant part of the depository consists of tissue samples of patients diagnosed with colorectal cancer 24% and stomach cancer 23% of the total number of tissue samples, while the number of tissue samples of pancreatic cancer is 10%, and esophageal cancer and breast cancer 22%. In addition to tissue samples, the biobank of the National Medical Research Centre for Oncology stores 24 cell lines of a human origin and the collection of 200 microbiota samples: 100 are from patients diagnosed with lung cancer and 100 from conditional healthy donors. Currently, the studies have been performed on biomaterial from the biobank build up collections to search for prognostic biomarkers and potential targets for targeted therapy by using high-throughput sequencing in patients diagnosed with pancreatic cancer and brain cancer. Thus, the collections play an important role for research in the field of personalized medicine, providing early diagnosis and effective treatment for each patient.
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