oncotomskСибирский онкологический журналSiberian journal of oncology1814-48612312-3168Tomsk National Research Medical Сепtеr of the Russian Academy of Sciences10.21294/1814-4861-2016-15-6-70-78oncotomsk-450Research ArticleОБЗОРЫREVIEWSМИКРОСАТЕЛЛИТНАЯ НЕСТАБИЛЬНОСТЬ КАК МОЛЕКУЛЯРНО-ГЕНЕТИЧЕСКИЙ МАРКЕР НАРУШЕНИЯ СИСТЕМЫ РЕПАРАЦИИ ОШИБОЧНО СПАРЕННЫХ НУКЛЕОТИДОВ ПРИ РАКЕ ПИЩЕВОДАMICROSATELLITE INSTABILITY AS A MOLECULAR GENETIC MARKER OF DEFECTIVE MISMATCH REPAIR SYSTEM IN ESOPHAGEAL CANCERКитО. И.KitО. I.

Кит Олег Иванович - доктор медицинских наук, профессор, директор РНИОИ.

344037, г. Ростов-на-Дону, ул. 14 линия, 63. E-mail: rnioi@list.ru. SPIN-код: 1728-0329

Kit Oleg I. - MD, DSc, Professor, Director.

63, 14 Line Street, 344037-Rostov-on-Don, Russia. E-mail: rnioi@list.ru. SPINcode: 1728-0329

rnioi@list.ruВодолажскийД. И.VodolazhskyD. I.

Водолажский Дмитрий Игоревич - кандидат биологических наук, руководитель лаборатории «Молекулярная онкология.

344037, г. Ростов-на-Дону, ул. 14 линия, 63. E-mail: dvodolazhsky@gmail.com. SPIN-код: 6660-5361

Vodolazhsky Dmitry I. - PhD, Head of Molecular Oncology Laboratory.

63, 14 Line Street, 344037-Rostov-on-Don, Russia. E-mail: dvodolazhsky@gmail.com. SPIN code: 6660-5361.

dvodolazhsky@gmail.comКолесниковЕ. Н.KolesnikovE. N.

Колесников Евгений Николаевич - кандидат медицинских наук, заведующий отделением абдоминальной онкологии.

344037, г. Ростов-на-Дону, ул. 14 линия, 63. E-mail: rnioi@list.ru. SPIN-код: 8434-6494

Kolesnikov Evgeny N. - MD, PhD, Head of  Abdominal Oncology Department.

63, 14 Line Street, 344037-Rostov-on-Don, Russia. E-mail: rnioi@list.ru. SPIN-code: 8434-6494

rnioi@list.ruТимошкинаН. Н.TimoshkinaN. N.

Тимошкина Наталья Николаевна - кандидат биологических наук, старший научный сотрудник лаборатории «Молекулярная онкология.

344037, г. Ростов-на-Дону, ул. 14 линия, 63. E-mail: n_timoshkina@mail.ru. SPIN-код: 9483-4330

Timoshkina Natalia N. - PhD, Senior Researcher, Molecular Oncology Laboratory.

63, 14 Line Street, 344037-Rostov-on-Don, Russia. E-mail: n_timoshkina@mail.ru. SPIN-code: 9483-4330

n_timoshkina@mail.ruЕфимоваИ. Ю.EfimovaI. Yu.

Ефимова Ирина Юрьевна - младший научный сотрудник лаборатории «Молекулярная онкология».

344037, г. Ростов-на-Дону, ул. 14 линия, 63. E-mail: 9889966451i@gmail.com. SPIN-код: 1982-5034

Efimova Irina Yu. - Junior Researcher, Molecular Oncology Laboratory.

63, 14 Line Street, 344037-Rostov-on-Don, Russia. E-mail: 9889966451i@gmail.com. SPIN-code: 1982-5034

9889966451i@gmail.comРостовский научно-исследовательский онкологический институтРоссияRostov Cancer Research InstituteRussian Federation2016291220161567078Copyright © Кит О.И., Водолажский Д.И., Колесников Е.Н., Тимошкина Н.Н., Ефимова И.Ю., 20162016Кит О.И., Водолажский Д.И., Колесников Е.Н., Тимошкина Н.Н., Ефимова И.Ю.Kit О.I., Vodolazhsky D.I., Kolesnikov E.N., Timoshkina N.N., Efimova I.Y.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.siboncoj.ru/jour/article/view/450

Рак пищевода (РП) является агрессивной по течению и прогнозу злокачественной эпителиальной опухолью. Аденокарцинома и плоскоклеточный рак относятся к наиболее распространенным гистотипам злокачественных новообразований пищевода с постоянной тенденцией к увеличению роста заболеваемости. Существующая система оценки риска развития онкопатологии с помощью эндоскопической биопсии, оставаясь общепризнанным «золотым стандартом» диагностики, приводит как к ложноположительным, так и ложноотрицательным результатам и поэтому нуждается в дополнительных методах предиктивной диагностики и выявлении фундаментальных механизмов онкотрансформации тканей. Молекулярные события, которые контролируют процессы малигнизации тканей пищевода, не полностью ясны, однако описаны несколько гистологических и одновременно генетических изменений, характерных для аденокарциномы и плоскоклеточного рака пищевода: аберрантные метилирование и копийность ДНК, изменение стабильности ДНК, её экспрессии и т. п. В настоящем обзоре обобщены исследования, направленные на изучение нестабильности генома клеток (микросателлитной нестабильности, MSI), трансформированных в опухолевые. Рассмотрены механизмы взаимодействия между комплексом мисматч-репарации и микро-РНК, NGS исследования микросателлитной нестабильности при раке пищевода. Последние достижения геномных и молекулярных исследований MSI+ раков могут успешно дополнить гистологический анализ на уровне предиктивной диагностики и помочь в разработке новых терапевтических подходов к лечению.

Esophageal cancer is an aggressive form of cancer. Adenocarcinoma and squamous cell carcinoma are the most common histological types of esophageal cancer, with the incidence rate showing an upward tendency. Although endoscopic biopsy is considered the «gold standard» for diagnosis of esophageal cancer, both falsepositive and false-negative results can occur, therefore, the predictive and prognostic molecular markers in outcome of esophageal cancer are required. Although the molecular events involved in esophageal cancer pathogenesis are still poor understood, there have been reports on histological and genetic changes, such as DNA aberrant methylation and copy number variation, changes in DNA stability, its expression and etc. This review summarizes various investigations aimed at studying genomic instability (microsatellite instability, MSI), which predisposes the cell to malignant transformation. The mechanisms of interaction between the mismatch repair and miRNA expression in esophageal cancer have been studied. Recent advances in genomic and molecular studies of MSI+ cancers can successfully complement the histological assessment and help to develop novel therapeutic approaches to cancer treatment.

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The authors declare that there are no conflicts of interest present.