cancerspЮжно-Российский онкологический журнал/ South Russian Journal of CancerSouth Russian Journal of Cancer2686-9039АНО "Перспективы онкологии"10.37748/2686-9039-2022-3-2-6cancersp-161Research ArticleОБЗОРЫREVIEWSПоказатель копийности генов у больных колоректальным раком как маркер клинического исхода заболевания и ответа на терапиюGenes copy number variation in colorectal cancer patients as a marker of the disease clinical outcome and response to therapyhttps://orcid.org/0000-0001-7328-8074МасловА. А.MaslovA. A.

Маслов Андрей Александрович – доктор медицинских наук, профессор, главный врач Ростов-на-Дону

SPIN: 5963-5915,

AuthorID: 817983

Andrey A. Maslov – Dr. Sci. (Med.), professor, chief doctor

Rostov-on-Don

SPIN: 5963-5915,

AuthorID: 817983

gabo80.80@inbox.ruhttps://orcid.org/0000-0001-8397-4393ЧалхахянЛ. Х.ChalkhakhyanL. Kh.

Чалхахян Лусеген Хачатурович – кандидат медицинских наук, хирург отделения абдоминальной онкологии № 2

344037, г. Ростов-на-Дону, ул. 14-я линия, д. 63

SPIN: 6534-5911,

AuthorID: 794696

Lusegen Kh. Chalkhakhyan – Cand. Sci. (Med.), surgeon at the abdominal oncology department No. 2

63 14 line str., Rostov-on-Don 344037

SPIN: 6534-5911,

AuthorID: 794696

gabo80.80@inbox.ruhttps://orcid.org/0000-0002-1220-7143МалининС. А.MalininS. A.

Малинин Сергей Андреевич – кандидат медицинских наук, онколог отделения абдоминальной онкологии № 2

Ростов-на-Дону

SPIN: 7229-1610, AuthorID: 794691

Sergey A. Malinin – Cand. Sci. (Med.), oncologist at the abdominal oncology department No. 2

Rostov-on-Don

SPIN: 7229-1610,

AuthorID: 794691

Serg-mail@mail.ruhttps://orcid.org/0000-0003-4905-4977КаминскийГ. В.KaminskyG. V.

Каминский Геннадий Владимирович – кандидат медицинских наук, хирург отделения абдоминальной онкологии № 2

Ростов-на-Дону

SPIN: 3308-4107,

AuthorID: 794670

Gennadii V. Kaminsky – Cand. Sci. (Med.), surgeon at the abdominal oncology department No.2

Rostov-on-Don

SPIN: 3308-4107,

AuthorID: 794670

kamdoc@mail.ruhttps://orcid.org/0000-0002-0328-9714МирзоянЭ. А.MirzoyanE. A.

Мирзоян Эллада Арменовна – аспирант

Ростов-на-Дону

SPIN: 2506-8605,

AuthorID: 1002948,

ResearcherID: AAZ-2780-2021,

Scopus Author ID: 57221118516

Ellada A. Mirzoyan – PhD student

Rostov-on-Don

SPIN: 2506-8605,

AuthorID: 1002948,

ResearcherID: AAZ-2780-2021,

Scopus Author ID: 57221118516

ellada.mirzoyan@yandex.ruНМИЦ онкологииРоссияNational Medical Research Centre for OncologyRussian Federation202219062022325264Copyright © Маслов А.А., Чалхахян Л.Х., Малинин С.А., Каминский Г.В., Мирзоян Э.А., 20222022Маслов А.А., Чалхахян Л.Х., Малинин С.А., Каминский Г.В., Мирзоян Э.А.Maslov A.A., Chalkhakhyan L.K., Malinin S.A., Kaminsky G.V., Mirzoyan E.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.cancersp.com/jour/article/view/161

Аномальная копийность генов – особый типом генетических полиморфизмов, является отличительной чертой большинства солидных опухолей, включая колоректальный рак. Аномальная копийность генов приводит к специфическому для опухоли геномному дисбалансу, который проявляется уже в предраковых поражениях-предшественниках. Целью данного обзора стала систематизация разобщенных данных о наблюдаемых при колоректальном раке изменениях копийности генов и их влиянии на исход заболевания и ответ на терапию. Были проанализированы данные 58 исследований по изменению числа копий генов и их экспрессии в первичных карциномах, клеточных линиях и экспериментальных моделях. В данном обзоре рассмотрен спектр генетических изменений, которые приводят к колоректальному раку, описаны наиболее частые изменения количества копий генов на разных стадиях заболевания, и изменения количества копий генов, которые потенциально могут повлиять на исход болезни отдельных пациентов или их ответ на проводимую терапию. Фактически, аберрантная копийность генов как форма хромосомного дисбаланса затрагивает целый ряд генов, обеспечивающих метаболическое избирательное преимущество для опухолевой клетки. Изменения числа копий генов у больных колоректальным раком не только положительно коррелируют с изменениями их экспрессии, но также влияют на уровни транскрипции генов в масштабе всего генома. Аберрантная копийность генов тесно связана с исходом заболевания и ответом на лечение 5 фторурацилом, иринотеканом, цетуксимабом и бевацизумабом. Тем не менее, возможность трансляции показателя копийности генов в клиническую практику требует дальнейших исследований.

Abnormal gene copies, a special type of genetic polymorphism, is a hallmark of most solid tumors, including colorectal cancer. Abnormal copy number of genes leads to tumor-specific genomic imbalance, which manifests itself already in precancerous precursor lesions. The aim of this review was to systematize the scattered data on changes in gene copy number observed in colorectal cancer and their impact on the outcome of the disease and response to therapy. The data from 58 studies was analyzed on gene copy number changes and their expression in primary carcinomas, cell lines and experimental models. This review examines the spectrum of genetic changes that lead to colorectal cancer, describes the most frequent changes in the number of gene copies at different stages of the disease, and changes in the number of gene copies that can potentially affect the outcome of the disease of individual patients or their response to therapy. In fact, aberrant gene copy number as a form of chromosomal imbalance affects a number of genes that provide a metabolic selective advantage for a tumor cell. Changes in the genes copy number in colorectal cancer patients not only positively correlate with changes in their expression, but also affect the levels of gene transcription at the genome-wide scale. Aberrant gene copy numbers are closely related to disease outcome and response to treatment with 5 fluorouracil, irinotecan, cetuximab and bevacizumab. Nevertheless, the possibility of translating the genes copy number index into clinical practice requires further research.

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