Abstract
Kidney cancer is a heterogeneous group of malignant tumors, the vast majority of which are renal cell carcinomas (RCC) of various morphological types, of which the most common is the clear cell renal cell carcinoma (ccRCC). Particular attention in the carcinogenesis of the ccRCC is given to a number of tumor suppressor genes located on the short arm of the third chromosome. One of these genes, which are inactivated in the case of ccRCC is the PBRM1 gene encoding the PBAF SWI/SNF subunit of the chromatin remodeling complex, BAF180. The PBRM1 gene is located on the short arm of the third chromosome in the 3p21 region near the von Hippel-Lindau gene (VHL), the mutation in which is the main event in the occurrence of ccRCC. The aim of our investigation is identification of changes in the nucleotide sequence of the PBRM1 tumor suppressor gene in patients with ccRCC. 210 pairs of DNA samples isolated from ccRCC tissue were studied. Analysis of changes in the nucleotide sequence of DNA was carried out by HRM analysis and direct sequencing. In the PBRM1 gene, two somatic mutations were found (c.233G>A (p.D45N) in exon 2, c.1675-1676delTC in exon 15) which were not described previously, and one known polymorphic variant rs17264436 (in exon 23). The frequency of detected mutations was 0.95 % of cases. Analysis of the allelic association for the polymorphic locus rs17264436 showed a statistically significant increase in the risk of developing advanced kidney cancer in carriers of allele rs17264436*A, which can be used in the development of prognostic marker panels. Perhaps the low frequency of mutations in the samples we studied is due to the fact that the inactivation of the PBRM1 gene takes place in other ways, and may also be due to the ethno-specificity of the studied group of patients.
Highlights
Identification of alterations in the nucleotide sequence of the chromatin remodeling gene polybromo gene 1 (PBRM1) in clear cell renal cell carcinoma patients
Kidney cancer is a heterogeneous group of malignant tumors, the vast majority of which are renal cell carcinomas (RCC) of various morphological types, of which the most common is the clear cell renal cell carcinoma
One of these genes, which are inactivated in the case of clear cell renal cell carcinoma (ccRCC) is the PBRM1 gene encoding the PBAF SWI/SNF subunit of the chromatin remodeling complex, BAF180
Summary
Целью настоящего ис следования был поиск изменений нуклеотидной последовательности гена-супрессора опухолевого роста PBRM1 у пациентов со светлоклеточным раком почки. Как цитировать эту статью: Климентова Е.А., Гилязова И.Р., Измайлов А.А., Султанов И.М., Бермишева М.А., Павлов В.Н., Хуснутдинова Э.К. Поиск изменений нуклеотидной последовательности гена ремоделирования хроматина PBRM1 у пациентов со светлоклеточным раком почки. Ген PBRM1 расположен на коротком плече третьей хромосомы в области 3р21 вблизи гена фон Хиппеля – Линдау (VHL), мутации в котором представляют собой основное событие при возникновении СРП (Audenet et al, 2011). Целью настоящего исследования был поиск изменений нуклеотидной последовательности в гене PBRM1 у пациентов со светлоклеточным раком почки башкирской, русской и татарской этнической принадлежности. Результаты В ходе анализа нуклеотидной последовательности во втором экзоне гена PBRM1 у пациента с метастатическим раком почки была обнаружена миссенс-мутация c.233G>A, которая приводит к замене аспарагиновой кислоты на аспарагин в 45-м положении белка (p.D45N). Ранее у этого пациента нами была впервые идентифицирована делеция семи нуклеотидов в 3-м экзоне гена фон Хиппеля – Линдау (VHL), (c.498_504del), которая также вела к сдвигу рамки считывания и образованию стоп-кодона (p.V166Vfs*1) (Кутлыева и др., 2012)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
