Almanac of Clinical MedicineAlmanac of Clinical MedicineАльманах клинической медицины2072-05052587-9294Moscow Regional Research and Clinical Institute (MONIKI)162610.18786/2072-0505-2022-50-002REVIEW ARTICLEОБЗОРReview ArticleMolecular genetic testing in colon cancer: clinical aspectsМолекулярно-генетическое тестирование рака толстой кишки: клинические аспектыhttps://orcid.org/0000-0002-7690-8328MartianovAleksandr S.МартьяновАлександр Сергеевич
Russian Federation

Postgraduate Student, Laboratory of Molecular Oncology

аспирант, научная лаборатория молекулярной онкологии

aleksandr.s.martianov@gmail.comhttps://orcid.org/0000-0002-2396-6540KuliginaEkaterina Sh.КулигинаЕкатерина Шотовна
Russian Federation

PhD (in Biol.), Senior Research Fellow, Laboratory of Molecular Oncology

канд. биол. наук, ст. науч. сотр., научная лаборатория молекулярной онкологии

kate.kuligina@gmail.comhttps://orcid.org/0000-0002-6549-8378RomankoAlexandr A.РоманькоАлександр Андреевич
Russian Federation

Clinical Research Assistant, Laboratory of Molecular Oncology, Postgraduate Student, Medical Technologists, Chair of General and Molecular Medical Genetics

лаборант-исследователь, научная лаборатория молекулярной онкологии, аспирант, медицинский лаборант, кафедра общей и молекулярной медицинской генетики

romanko.aleksandr.a@gmail.comhttps://orcid.org/0000-0003-4529-7891ImyanitovEvgeny N.ИмянитовЕвгений Наумович
Russian Federation

MD, PhD, Professor, Corr. Member of Russ. Acad. Sci., Head of Science Department of Tumor Growth Biology, Head of Chair of General and Molecular Medical Genetics

д-р мед. наук, профессор, чл.-корр. РАН, заведующий научным отделом биологии опухолевого роста, заведующий кафедрой общей и молекулярной медицинской генетики

evgeny@imyanitov.spb.ruN.N. Petrov National Medicine Research Center of OncologyФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Петрова» Минздрава РоссииSt. Petersburg State Pediatric Medical UniversityФГБОУ ВО «Санкт-Петербургский государственный педиатрический медицинский университет» Минздрава России23022022280420225011121001202223022022Copyright ©; 2022, Martianov A.S., Kuligina E.S., Romanko A.A., Imyanitov E.N.Copyright ©; 2022, Мартьянов А.С., Кулигина Е.Ш., Романько А.А., Имянитов Е.Н.2022Martianov A.S., Kuligina E.S., Romanko A.A., Imyanitov E.N.Мартьянов А.С., Кулигина Е.Ш., Романько А.А., Имянитов Е.Н.https://creativecommons.org/licenses/by-nc/4.0https://almclinmed.ru/jour/article/view/1626

Molecular genetic diagnostics is an essential element to plan for management of colorectal cancer (CRC) patients. The choice of systemic treatment for CRC is impossible without molecular testing of the tumor. For instance, the assessment of the KRAS and NRAS genes is mandatory for consideration of anti-EGFR agents. Tumors with BRAF V600E mutation are characterized by aggressive behavior, the necessity of intensive cytostatic regimens, as well as by sensitivity to combination therapy with BRAF and EGFR inhibitors. Inactivation of the DNA mismatch repair, the MUTYH gene or DNA polymerase epsilon (POLE) leads to an excessive tumor mutational burden; these CRC types are highly immunogenic and therefore respond to immune checkpoint inhibitors. Some colorectal carcinomas are characterized by overexpression of the HER2 oncogene, which make them sensitive to corresponding target therapies. There are CRCs with clinical signs of hereditary predisposition, which require germline genetic testing. Nowadays the molecular diagnosis of CRC is being seriously modified due to worldwide implementation of the next-generation sequencing (NGS) and hypersensitive variants of polymerase chain reaction, for example, droplet digital polymerase chain reaction (ddPCR). Non-invasive liquid biopsy is an example of another highly useful innovation that has growing importance for CRC screening, control of surgical intervention efficacy and monitoring of the disease course.

Молекулярно-генетическая диагностика – неотъемлемый элемент планирования лечения пациентов с раком толстой кишки (РТК). Выбор системной терапии при РТК невозможен без молекулярного тестирования опухоли. Так, оценка статуса генов KRAS и NRAS обязательна при рассмотрении вопроса о назначении анти-EGFR терапии. Опухоли с мутацией BRAF V600E характеризуются агрессивным поведением, необходимостью использования интенсивных режимов цитостатической терапии, а также чувствительностью к комбинированной терапии ингибиторами BRAF и EGFR. Инактивация генов системы репарации неспаренных оснований ДНК (англ. mismatch repair, MMR), гена MUTYH или ДНК-полимеразы эпсилон (POLE) приводит к чрезмерной мутационной нагрузке опухоли; такие виды РТК обладают высокой иммуногенностью и поэтому отвечают на лечение ингибиторами контрольных точек иммунного ответа. У некоторых колоректальных карцином отмечается гиперэкспрессия онкогена HER2, что определяет их чувствительность к соответствующей таргетной терапии. Существуют РТК с клиническими признаками наследственной предрасположенности к этому заболеванию – в таких случаях для выявления наследственных форм необходимо проведение генетического тестирования. Сегодня молекулярная диагностика РТК претерпевает серьезные изменения в связи с повсеместным внедрением секвенирования нового поколения (англ. next-generation sequencing, NGS) и сверхчувствительных модификаций полимеразной цепной реакции (например, цифровой капельной, ddPCR). Неинвазивная жидкостная биопсия – еще одно крайне полезное нововведение, которое имеет растущее значение при скрининге РТК, контроле эффективности хирургического вмешательства и мониторинге течения заболевания.

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