СОВРЕМЕННЫЕ ПРЕДСТАВЛЕНИЯ О МОЛЕКУЛЯРНЫХ МЕХАНИЗМАХ В ОНКОГЕНЕЗЕ ГАСТРОИНТЕСТИНАЛЬНЫХ СТРОМАЛЬНЫХ ОПУХОЛЕЙ
PDF

Ключевые слова

ГАСТРОИНТЕСТИНАЛЬ НЫЕ СТРОМАЛЬНЫЕ ОПУХОЛИ
ДИСТРОФИН

Аннотация

Ассоциация генетических драйверных изменений в гастроинтестинальных стромальных опухолях (ГИСО) с клиническими последствиями является наиболее изученным аспектом в биологии солидных опухолей. Генотипирование отдельных экзонов cKIT и PDGFRA вошло в стандартную практику диагностики и лечения ГИСО. В обзоре проведен анализ современных представлений о молекулярно-генетических механизмах и маркерах, лежащих в основе профилирования ГИСО. Особый интерес представляют опухоли дикого типа по c-KIT и PDGFRA, в которых обнаруживают активирующие мутации онкогенов RAS, BRAF и EGFR, ассоциированные с ранними стадиями прогрессирования заболевания. Приведены данные исследований генетических и эпигенетических изменений при ГИСО, выявивших прогностическое значение инактивации CDKN2A и р53, делеций 22q, 1p и 15q, CpG-гиперметилирования. Описаны новые факторы, определяющие высокий риск прогрессирования ГИСО: инактивация дистрофина, гипометилирование ДНК, изменение экспрессии микрорнк и HOTAIR. Достигнутый прогресс в понимании молекулярных механизмов гисо открывает возможность разработки и эффективного применения новых терапевтических подходов, расширения спектра молекулярно-генетических маркеров, определяющих тактику ведения больных.

https://doi.org/10.37469/0507-3758-2020-66-1-13-22
PDF

Библиографические ссылки

Søreide K., Sandvik O.M., Søreide J.A. et al. Global epidemiology of gastrointestinal stromal tumours (GIST): A systematic review of population-based cohort studies // Cancer epidemiology. - 2016. - Vol. 40. - P. 39-46.

Yamamoto H., Oda Y Gastrointestinal stromal tumor: recent advances in pathology and genetics // Pathology international. - 2015. - Vol. 65(1). - P. 9-18.

Rossi S., Miceli R., Messerini L. et al. Natural history of imatinib-naive GISTs: a retrospective analysis of 929 cases with long-term follow-up and development of a survival nomogram based on mitotic index and size as continuous variables // The American journal of surgical pathology. - 2011. - Vol. 35(11). - P 1646-1656.

Кит О.И., Колесников Е.Н., Снежко А.В. и др. Случай успешного лечения рецидивной гастроинтестинальной стромальной опухоли двенадцатиперстной кишки с инвазией в нижнюю полую вену // Онкология. Журнал им. П.А.Герцена. - 2016. - № 4. - С.58-62.

Hemming M.L., Heinrich M.C., Bauer S., George S. Translational insights into gastrointestinal stromal tumor and current clinical advances // Annals of Oncology. - 2018. - Vol. 29(10). - P. 2037-2045.

Carney J.A., Stratakis C.A. Familial paraganglioma and gastric stromal sarcoma: a new syndrome distinct from the Carney triad // American journal of medical genetics. - 2002. - Vol. 108(2). - P. 132-139.

Gopie P., Mei L., Faber A.C. et al. Classification of gastrointestinal stromal tumor syndromes // Endocrine-related cancer. - 2018. - Vol. 25(2). - P. R49-R58.

Burgoyne A.M., Somaiah N., Sicklick J.K. Gastrointestinal stromal tumors in the setting of multiple tumor syndromes // Current opinion in oncology. - 2014. - Vol. 26(4). - P. 408-414.

Forde P.M., Cochran R.L., Boikos S.A. et al. Familial GI Stromal Tumor With Loss of Heterozygosity and Amplification of Mutant KIT // Journal of clinical oncology: official journal of the American Society of Clinical Oncology. - 2016. - Vol. 34(3). - P. e13.

Roskoski Jr. R. The role of small molecule Kit protein-tyrosine kinase inhibitors in the treatment of neoplastic disorders // Pharmacological research. - 2018. - Vol. 133. - P. 35-52.

Ahmad F., Lad P., Bhatia S., Das B.R. et al. Molecular spectrum of c-KIT and PDGFRA gene mutations in gastro intestinal stromal tumor: Determination of frequency, distribution pattern and identification of novel mutations in Indian patients // Medical Oncology. - 2015. - Vol. 32(1). - P. 424.

Obata Y., Horikawa K., Takahashi T. et al. Oncogenic signaling by Kit tyrosine kinase occurs selectively on the Golgi apparatus in gastrointestinal stromal tumors // Oncogene. - 2017. - Vol. 36(26). - P. 3661-3672.

Babaei M.A., Kamalidehghan B., Saleem M. et al. Receptor tyrosine kinase (c-Kit) inhibitors: a potential therapeutic target in cancer cells // Drug design, development and therapy. - 2016. - Vol. 10. - P. 2443-2459.

Andrae J., Gallini R., Betsholtz C. Role of platelet-derived growth factors in physiology and medicine. Genes Dev. - 2008. - Vol. 22. - P. 1276-1312.

Liang J., Wu YL., Chen B.J. et al. The C-kit receptor-mediated signal transduction and tumor-related diseases // International journal of biological sciences. - 2013. - Vol. 9(5). - P. 435-443.

Gajiwala K.S., Wu J.C., Christensen J. et al. KIT kinase mutants show unique mechanisms of drug resistance to imatinib and sunitinib in gastrointestinal stromal tumor patients // Proceedings of the National Academy of Sciences. - 2009. - Vol. 106(5). - P. 1542-1547.

Wozniak A., Rutkowski P., Schffski P. et al. Tumor genotype is an independent prognostic factor in primary gastrointestinal stromal tumors of gastric origin: a european multicenter analysis based on ConticaGIST // Clinical cancer research. - 2014. - Vol. 20(23). - P. 6105-6116.

Мазуренко H.H., Цыганова И.В. Молекулярно-генетические особенности и маркеры гастроинтестинальных стромальных опухолей // Успехи молекулярной онкологии. - 2015. - № 2. - C. 29-40.

Steigen S.E., Eide T.J., Wasag B. et al. Mutations in gastrointestinal stromal tumors-a population based study from Northern Norway // Apmis. - 2007. - Vol. 115(4). - P. 289-298.

Chen L.L., Holden J.A., Choi H et al. Evolution from heterozygous to homozygous KIT mutation in gastro-intestinal stromal tumour correlates with the mechanism of mitotic nondisjunction and significant tumour progression // Mod. Pathol. - 2008. - Vol. 21. - P. 826-836.

Antonescu C.R., Sommer G., Sarran L. et al. Association of KIT exon 9 mutations with nongastric primary site and aggressive behavior: KIT mutation analysis and clinical correlates of 120 gastrointestinal stromal tumors // Clinical Cancer Research. - 2003. - Vol. 9(9). - P. 3329-3337.

Lasota J., Miettinen M. KIT and PDGFRA mutations in gastrointestinal stromal tumors (GISTs) // Seminars in diagnostic pathology. - 2006. - Vol. 23(2). - P. 91-102.

Szucs Z., Thway K., Fisher C. et al. Molecular subtypes of gastrointestinal stromal tumors and their prognostic and therapeutic implications // Future Oncology. - 2017. - Vol. 13(1). - P. 93-107.

Miranda C., Nucifora M., Molinari F. et al. KRAS and BRAF mutations predict primary resistance to imatinib in gastrointestinal stromal tumors // Clinical cancer research. - 2012. - Vol. 18(6). - P. 1769-1776.

Melzer C., Hass R., Lehnert H., Ungefroren H. RAC1B: A Rho GTPase with versatile functions in malignant transformation and tumor progression // Cells. - 2019. - Vol. 8(1). - P. 21.

Huss S., Pasternack H., Ihle M.A. et al. Clinicopathological and molecular features of a large cohort of gastrointestinal stromal tumors (GISTs) and review of the literature: BRAF mutations in KIT/PDGFRA wild-type GISTs are rare events // Human pathology. - 2017. - Vol. 62. - P. 206-214.

Mou Y., Wang Q., Li B. The "Wild"-type gastrointestinal stromal tumors: Heterogeneity on molecule characteristics and clinical features // Cancer Translational Medicine. - 2018. - Vol. 4(3). - P. 75-82.

Li K., Cheng H., Li Z. et al. Genetic progression in gastrointestinal stromal tumors: mechanisms and molecular interventions // Oncotarget. - 2017. - Vol. 8(36). - P. 60589-60604.

Schaefer I.-M., Wang Y, Liang C.-W. et al. MAX inactivation is an early event in GIST development that regulates p16 and cell proliferation // Nature communications. - 2017. - Vol. 8. - P. 14674-14679.

Pantaleo M.A., Urbini M., Indio V. et al. Genome-wide analysis identifies MEN1 and MAX mutations and a neuroendocrine-like molecular heterogeneity in quadruple WT GIST // Molecular Cancer Research. - 2017. - Vol. 15(5). - P. 553-562.

Ihle M.A., Huss S., Jeske W. et al. Expression of cell cycle regulators and frequency of TP53 mutations in high risk gastrointestinal stromal tumors prior to adjuvant imatinib treatment // PloS one. - 2018. - Vol. 13(2). - P. e0193048.

Heinrich M.C., Patterson J., Beadling C. et al. Genomic aberrations in cell cycle genes predict progression of KITmutant gastrointestinal stromal tumors (GISTs) // Clinical Sarcoma Research. - 2019. - Vol. 9(1). - P. 3.

Wang Y., Fletcher J. A. Cell Cycle and dystrophin dysregulation in GIST // Cell Cycle. - 2015. - Vol. 14(17). - P. 2713-2714.

Shi E., Chmielecki J., Tang C.M. et al. FGFR1 and NTRK3 actionable alterations in "Wild-Type" gastrointestinal stromal tumors // Journal of translational medicine. - 2016. - Vol. 14(1). - P. 339.

Amatu A., Sartore-Bianchi A., Siena S. NTRK gene fusions as novel targets of cancer therapy across multiple tumour types // ESMO open. - 2016. - Vol. 1(2). - P. e000023.

Toda-Ishii M., Akaike K., Suehara Y et al. Clinicopathological effects of protein phosphatase 2, regulatory subunit A, alpha mutations in gastrointestinal stromal tumors // Modern Pathology. - 2016. - Vol. 29(11). - P. 1424-1432.

Niinuma T., Kai M., Kitajima H. et al. Downregulation of miR-186 is associated with metastatic recurrence of gastrointestinal stromal tumors // Oncology letters. - 2017. - Vol. 14(5). - P. 5703-5710.

Schaefer I.M., Marino-Enriquez A., Fletcher J.A. What is new in gastrointestinal stromal tumor? // Advances in anatomic pathology. - 2017. - Vol. 24(5). - P. 259-267.

Ricci R., Saragoni L. Everything you always wanted to know about GIST (but were afraid to ask) // Pathologica. - 2016. - Vol. 108. - P. 90-103.

Fouquin A., Guirouilh-Barbat J., Lopez B. et al. PARP2 controls double-strand break repair pathway choice by limiting 53BP1 accumulation at DNA damage sites and promoting end-resection // Nucleic acids research. - 2017. - Vol. 45(21). - P. 12325-12339.

Pei D.S., Jia P.P., Luo J.J. et al. AP endonuclease 1 (Apex1) influences brain development linking oxidative stress and DNA repair // Cell death & disease. - 2019. - Vol. 10(5). - P. 348-361.

Xu X., Li J., Sun X., Guo Y et al. Tumor suppressor NDRG2 inhibits glycolysis and glutaminolysis in colorectal cancer cells by repressing c-Myc expression // Oncotarget. - 2015. - Vol. 6(28). - P. 26161-26176.

Brull A., Morales Rodriguez B., Bonne G. et al. The pathogenesis and therapies of striated muscle laminopathies // Frontiers in physiology. - 2018. - Vol. 9. - P. 1533.

Petrilli A.M., Fernandez-Valle C. Role of Merlin/NF2 inactivation in tumor biology // Oncogene. - 2016. - Vol. 35(5). - P. 537-548.

Iorio N., Sawaya R.A., Friedenberg F.K. The biology, diagnosis and management of gastrointestinal stromal tumours // Alimentary pharmacology & therapeutics. - 2014. - Vol. 39(12). - P. 1376-1386.

Saito K., Sakurai S., Sano T. et al. Aberrant methylation status of known methylation-sensitive CpG islands in gastrointestinal stromal tumors without any correlation to the state of c-kit and PDGFRA gene mutations and their malignancy // Cancer science. - 2008. - Vol. 99(2). - P. 253-259.

Kojima K., Nakamura T., Ooizumi Y et al. Clinical significance of cancer specific methylation of the CDO1 gene in small bowel cancer // PloS one. - 2019. - Vol. 14(1). - P. e0211108.

Yang J., Ikezoe T., Nishioka C. et al. Long-term exposure of gastrointestinal stromal tumor cells to sunitinib induces epigenetic silencing of the PTEN gene // International journal of cancer. - 2012. - Vol. 130(4). - P. 959-966.

Bure I., Braun A., Kayser C. et al. The expression of hematopoietic progenitor cell antigen CD34 is regulated by DNA methylation in a site-dependent manner in gastrointestinal stromal tumours // International journal of cancer. - 2017. - Vol. 141(11). - P. 2296-2304.

Isosaka M., Niinuma T., Nojima M. et al. A screen for epi-genetically silenced microRNA genes in gastrointestinal stromal tumors // PloS one. - 2015. - Vol. 10(7). - P. e0133754.

Basilio-de-Oliveira R.P., Pannain V.L.N. Prognostic angiogenic markers (endoglin, VEGF, CD31) and tumor cell proliferation (Ki67) for gastrointestinal stromal tumors // World journal of gastroenterology: WJG. - 2015. - Vol. 21(22). - P. 6924-6930.

Haller F., Zhang J.D., Moskalev E.A. et al. Combined DNA methylation and gene expression profiling in gastrointestinal stromal tumors reveals hypomethylation of SPP1 as an independent prognostic factor // International journal of cancer. - 2015. - Vol. 136(5). - P. 1013-1023.

Huang K.K., McPherson J.R., Tay S.T. et al. SETD2 histone modifier loss in aggressive GI stromal tumours // Gut. - 2016. - Vol. 65(12). - P. 1960-1972.

Vidigal J. A., Ventura A. The biological functions of miR-NAs: lessons from in vivo studies // Trends in cell biology. - 2015. - Vol. 25(3). - P. 137-147.

Gyvyte U., Juzenas S., Salteniene V. et al. MiRNA profiling of gastrointestinal stromal tumors by next-generation sequencing // Oncotarget. - 2017. - Vol. 8(23). - P. 37225-37238.

Yamamoto H., Kohashi K., Fujita A., Oda Y et al. Fascin-1 overexpression and miR-133b downregulation in the progression of gastrointestinal stromal tumor // Modern Pathology. - 2013. - Vol. 26(4). - P 563-571.

Akakaya P., Caramuta S., hlen J. et al. MicroRNAs and gastrointestinal stromal tumor // microRNA: Cancer. - 2015. - P 51-70.

Koelz M., Lense J., Wrba F. et al. Down-regulation of miR-221 and miR-222 correlates with pronounced Kit expression in gastrointestinal stromal tumors // International journal of oncology. - 2011. - Vol. 38(2). - P. 503-511.

Gits C.M., van Kuijk PF., Jonkers M.B. et al. MiR-17-92 and miR-221/222 cluster members target KIT and ETV1 in human gastrointestinal stromal tumours // British journal of cancer. - 2013. - Vol. 109(6). - P. 1625-1635.

Kim W.K., Park M., Kim YK. et al. MicroRNA-494 down-regulates KIT and inhibits gastrointestinal stromal tumor cell proliferation // Clinical cancer research. - 2011. - Vol. 17(24). - P. 7584-7594.

Fang Y, Fullwood M. J. Roles, functions, and mechanisms of long non-coding RNAs in cancer // Genomics, proteomics & bioinformatics. - 2016. - Vol. 14(1). - P. 42-54.

Tang Q., Hann S. S. HOTAIR: an oncogenic long noncoding RNA in human cancer // Cellular Physiology and Biochemistry. - 2018. - Vol. 47(3). - P. 893-913.

Bhan A., Mandal S. S. LncRNA HOTAIR: A master regulator of chromatin dynamics and cancer // Biochimica et Biophysica Acta (BBA)-Reviews on Cancer. - 2015. - Vol. 1856(1). - P 151-164.

Niinuma T, Suzuki H., Nojima M. et al. Upregulation of miR-196a and HOTAIR drive malignant character in gastrointestinal stromal tumors // Cancer research. - 2012. - Vol. 72(5). - P 1126-1136.

Lee N.K., Lee J.H., Kim W.K. et al. Promoter methylation of PCDH10 by HOTAIR regulates the progression of gastrointestinal stromal tumors // Oncotarget. - 2016. - Vol. 7(46). - P 75307-75318.

Jiang M.C. CAS (CSE1L) signaling pathway in tumor progression and its potential as a biomarker and target for targeted therapy // Tumour Biol. 2016. - Vol. 37(10). - P. 13077-13090.

Lowell C.A. Src-family and Syk kinases in activating and inhibitory pathways in innate immune cells: signaling cross talk // Cold Spring Harb Perspect Biol. - 2011. - Vol. 3(3). - P. a002352.

Cardoso H.J., Figueira M.I., Socorro S. The stem cell factor (SCF)/c-KIT signalling in testis and prostate cancer // J. Cell Commun Signal. - 2017. - Vol. 11(4). - P. 297-307.

Pennock S., Kim L.A., Kazlauskas A. Vascular Endothelial Cell Growth Factor A Acts via Platelet-Derived Growth Factor Receptor a To Promote Viability of Cells Enduring Hypoxia // Mol Cell Biol. - 2016. - Vol. 36(18). - P. 2314-2327.

Imura M., Kojima Y., Kubota Y. et al. Regulation of cell proliferation through a KIT-mediated mechanism in benign prostatic hyperplasia // Prostate. - 2012. - Vol. 72(14). - P 1506-1513.

Lennartsson J., Rönnstrand L. Stem cell factor receptor/ c-Kit: from basic science to clinical implications // Physiol Rev. - 2012. - Vol. 92(4). - P 1619-1649.

Plattner R., Irvin B.J., Guo S. et al. A new link between the c-Abl tyrosine kinase and phosphoinositide signalling through PLC-gamma1 // Nat Cell Biol. - 2003. - Vol. 5(4). - P 309-319.

Schlessinger J., Mohammadi M., Margolis B., Ullrich A. Role of SH2-containing proteins in cellular signaling by receptor tyrosine kinases // Cold Spring Harb Symp Quant Biol. - 1992. - Vol. 57. - P. 67-74.

Berridge M.J. Cell Signalling Biology. - 2014. - DOI: 10.1042/csb0001012

Лицензия Creative Commons

Это произведение доступно по лицензии Creative Commons «Attribution-NonCommercial-NoDerivatives» («Атрибуция — Некоммерческое использование — Без производных произведений») 4.0 Всемирная.

Copyright (c) 2020 Дмитрий Гвалдин, Екатерина Омельчук, Наталья Тимошкина, Владимир Трифанов, Юрий Сидоренко