tumorsMalignant tumoursMalignant tumours2224-50572587-6813Rosoncoweb10.18027/2224-5057-2017-2-6-13tumors-334Research ArticleФУНДАМЕНТАЛЬНАЯ ОНКОЛОГИЯ И ЭКСПЕРИМЕНТАЛЬНАЯ МЕДИЦИНАFUNDAMENTAL ONCOLOGY AND EXPERIMENTAL MEDICINEИзучение конкордантности мутационного статуса генов KRAS, NRAS, BRAF, PIK3CA между первичной опухолью и метастазами рака толстой кишкиConcordance of KRAS, NRAS, BRAF, PIK3CA mutation status between the primary tumor and metastases in patients with colorectal cancerФедянинМ. Ю.FedyaninM. Y.

к.м.н., с.н.с. отделения клинической фармакологии и химиотерапии

MD, PhD, Department of Clinical Pharmacology and Chemotherapy

fedianinmu@mail.ruСтрогоноваА. М.StrogonovaA. M.

к.м.н., с.н.с. отдела патологической анатомии опухолей человека

MD, PhD, Department of Pathomorphology

СендеровичА. И.SenderovichA. I.

к.м.н., н.с. отдела патологической анатомии опухолей человека

MD, PhD, Department of Pathomorphology

ДранкоС. Л.DrankoS. L.

м.н.с. отдела патологической анатомии опухолей человека

MD, Department of Pathomorphology

КозловН. А.KozlovN. A.

к.м.н., и. о. заведующего отдела патологической анатомии опухолей человека

MD, PhD, Department of Pathomorphology

ТрякинА. А.TryakinA. A.

д.м.н., и. о. заведующего отделением комбинированных методов лечения опухолей

MD, PhD, Department of Combined Tumor Treatments

СехинаО. В.SehinaO. V.

к.м.н., н.с. отделения клинической фармакологии и химиотерапии

MD, PhD, Department of Clinical Pharmacology and Chemotherapy

ЭльснукаеваХ.Х. М.ElsnukaevaH.H. M.

ординатор отделения клинической фармакологии и химиотерапи

MD, Department of Clinical Pharmacology and Chemotherapy

БулановА. А.BulanovA. A.

к.м.н., с.н.с. отделения клинической фармакологии и химиотерапии

MD, PhD, Department of Clinical Pharmacology and Chemotherapy

ПокатаевИ. А.PokataevI. A.

к.м.н., с.н.с., отделения клинической фармакологии и химиотерапии

MD, PhD, Department of Clinical Pharmacology and Chemotherapy

ПодлужныйД. В.PodlujniiD. V.

к.м.н., и. о. заведующего хирургическим отделения опухолей печени и поджелудочной железы

MD, PhD, Department of Liver Surgery

ГордеевС. С.GordeevS. S.

к.м.н., с.н.с. хирургического отделения проктологии

MD, PhD, Department of Coloproctological Surgery

РасуловА. О.RasulovA. O.

д.м.н., заведующий хирургическим отделением проктологии

MD, PhD, Department of Coloproctological Surgery

ТюляндинС. А.TjulandinS. A.

д.м.н., профессор, заведующий отделением клинической фармакологии и химиотерапии

prof., MD, PhD, Department of Clinical Pharmacology and Chemotherapy

НИИ клинической онкологии ФГБУ «РОНЦ им. Н. Н. Блохина», МоскваРоссияN. N. Blokhin Russian Cancer Research Center, MoscowRussian Federation20172007201702613Copyright © Федянин М.Ю., Строгонова А.М., Сендерович А.И., Дранко С.Л., Козлов Н.А., Трякин А.А., Сехина О.В., Эльснукаева Х.М., Буланов А.А., Покатаев И.А., Подлужный Д.В., Гордеев С.С., Расулов А.О., Тюляндин С.А., 20172017Федянин М.Ю., Строгонова А.М., Сендерович А.И., Дранко С.Л., Козлов Н.А., Трякин А.А., Сехина О.В., Эльснукаева Х.М., Буланов А.А., Покатаев И.А., Подлужный Д.В., Гордеев С.С., Расулов А.О., Тюляндин С.А.Fedyanin M.Y., Strogonova A.M., Senderovich A.I., Dranko S.L., Kozlov N.A., Tryakin A.A., Sehina O.V., Elsnukaeva H.M., Bulanov A.A., Pokataev I.A., Podlujnii D.V., Gordeev S.S., Rasulov A.O., Tjulandin S.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.malignanttumors.org/jour/article/view/334Цель

Цель. Целью настоящего исследования стало изучение факторов, ассоциированных с дискордантностью мутационного статуса генов KRAS, NRAS, BRAF, PIK3CA между первичной опухолью и метастазами рака толстой кишки.

Материалы и методы

Материалы и методы.  был проведен анализ ДНК методом плавления с TaqMan зондами с последующим секвенированием по Sanger для выявления мутаций в горячих точках 2 и 3 экзонов гена KRAS, 2 и 3 экзонов гена NRAS, 15 экзона гена BRAF и 9 и 20 экзонов гена PIK3CA в 148 образцах опухоли 65 пациентов (65 первичных опухолей и 83 метастаза).

Результаты

Результаты. мутации в генах KRAS, NRAS, PIK3CA и BRAF в первичной опухоли выявлены у 43,1%, 3,1%, 13,8% и 3,1% соответственно. Различия в мутационном статусе генов между первичной опухолью и метастазами выявлены у 29,2% пациентов: 16,9% – в гене KRAS, 3% – в NRAS, 12,3% – в PIK3CA и 3% – в BRAF. Дискордантность по мутационному статусу генов отмечена при локализации метастазов в головном мозге (p=0,02) и по брюшине (p=0,02). С увеличением времени между удалением первичной опухоли и метастазов увеличивалась и частота случаев расхождения по мутационному статусу генов. Связи дискордантности с другими клиническими и морфологическими факторами установить не удалось.

Вывод

Вывод. изменения мутационного статуса генов, особенно при длительном течении болезни, ставит вопрос о необходимости выполнения повторных биопсий при прогрессировании заболевания с целью определения мутационного статуса опухоли, которую мы в данный момент лечим. 

Introduction

Introduction. The concordance of KRAS gene mutation status between the primary and metastatic CRC is 95%. The aim of this study was to find factors associated with the disconcordance of KRAS, NRAS, BRAF, PIK3CA mutation status between the primary tumors and metastases in pts with CRC.

Patients and methods

Patients and methods. We performed DNA melting analysis with TaqMan probes and following Sanger sequencing to detect mutation hot-spots in KRAS exons 2 and 3, NRAS exons 2 and 3, BRAF exon 15, PIK3CA exons 9 and 20 in 148 tumor tissues from 65 pts (65 primary tumors and 83 metastases).

Results

Results. Mutations in KRAS, NRAS, PIK3CA and BRAF genes in primary tumors were detected in 43.1%, 3.1%, 13.8% and 3.1%, respectively. Discordance of mutation status of genes was identified in 29.2% of patients: 16.9% in KRAS, 3% in NRAS, 12.3% in PIK3CA and 3% BRAF status. In all cases of metastases in the brain we found the discordance in KRAS and PIK3CA mutation status (p=0.08). Also, peritoneal metastases had discordance in KRAS status (p=0.02). With the increase of period from removal of the primary tumor and metastases, the incidence rate of changes in the mutational status of the genes also increased.

Conclusion

Conclusion. discordance of the mutational status of genes, especially in the long course of the disease, raises the question of repeating biopsies in the progression of the disease 

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