Cancer UrologyCancer UrologyОнкоурология1726-97761996-1812Publishing House ABV Press41210.17650/1726-9776-2015-1-12-19LECTUREЛЕКЦИЯTesticular germ cell tumors: Molecular genetic and clinicomorphological aspectsМолекулярно-генетические и клинико-морфологические аспекты герминогенных опухолей яичкаNemtsovaM. V.НемцоваМ. В.
Russian Federation
nemtsova_m_v@mail.ruAndreevaYu. Yu.АндрееваЮ. Ю.
Russian Federation
Russian Academy of Postgraduate Education, Ministry of Health of RussiaГБОУ ДПО РМАПО Минздрава России 123 995 Москва, ул. Баррикадная, 2/12/1, Barrikadnaya St., Moscow 125 995, RussiaГБОУ ДПО РМАПО Минздрава России 123 995 Москва, ул. Баррикадная, 2/1Russian Academy of Postgraduate Education, Ministry of Health of Russia2/1, Barrikadnaya St., Moscow 125 995, Russia3003201511112193003201530032015https://oncourology.abvpress.ru/oncur/article/view/412

Testicular tumors are the most common form of solid cancer in young men. According to the 2004 WHO classification, testicular germ cell tumors (TGCT) may present with different histological types. Embryonic cells of varying grade may be a source of TGCT and the occurrence of this type of tumors is directly related to the formation of a pool of male sex cells and gametogenesis. The paper gives information on mo- lecular stages for the process of formation of male sex cells in health, as well as ways of their impairments leading to TGCT. An investigation of the profiles of gene expression and the spectrum of molecular damages revealed genes responsible for a predisposition to the sporadic and hereditary forms of TGCT.

The paper presents the current molecular genetic and clinicomorphological characteristics of TGCT. 

Опухоли яичка являются наиболее частой формой солидного рака у молодых мужчин. По классификации ВОЗ 2004 г. герминогенные опухоли яичка (ГОЯ) представлены различными гистологическими типами. Источником ГОЯ могут быть эмбриональные клетки различной степени дифференцировки, и появление опухолей этого типа напрямую связано с формированием пула мужских половых клеток и гаметогенезом. В статье приведены сведения о молекулярных этапах процесса формирования мужских половых клеток в норме, а также пути их нарушения, приводящие к появлению ГОЯ. В результате исследования профилей генной экспрессии и спек- тра молекулярных повреждений выявлены гены, определяющие предрасположенность к спорадическим и наследственным формам ГОЯ. В статье представлены современные молекулярно-генетические и клинико-морфологические характеристики ГОЯ. 

testicular germ cell tumorsprimary sex cellsstem cellsgenesexpressionmutationsseminomanonseminomateratomatro- phoblastic tumorchoriocarcinomaгерминогенные опухоли яичкапервичные половые клеткистволовые клеткигеныэкспрессиямутациисеминоманесеминоматератоматрофобластическая опухольхориокарцинома1. Berney D.M., Lee A., Shamash J. et al. The frequency and distribution of intratubular trophoblast in association with germ cell tumors of the testis. Am J Surg Pathol 2005;29:1300–3.Berney D.M., Lee A., Shamash J. et al. The frequency and distribution of intratubular trophoblast in association with germ cell tumors of the testis. Am J Surg Pathol 2005;29:1300–3.2. Eble J.N. Spermatocytic seminoma. Hum Pathol 1994;25:1035–42.Eble J.N. Spermatocytic seminoma. Hum Pathol 1994;25:1035–42.3. Burke A.P., Mostofi F.K. Spermatocytic seminoma: a clinicopathologic study of 79 cases. J Urol Pathol 1993;1:21–32.Burke A.P., Mostofi F.K. Spermatocytic seminoma: a clinicopathologic study of 79 cases. J Urol Pathol 1993;1:21–32.4. Kay R. Prepubertal testicular tumor registry. J Urol 1993;150:671–4.Kay R. Prepubertal testicular tumor registry. J Urol 1993;150:671–4.5. Francis R., Bower M., Brunstrom G. et al. Surveillance for stage I testicular germ cell tumours: results and cost benefit analysis of management options. Eur J Cancer 2000;36:1925–32.Francis R., Bower M., Brunstrom G. et al. Surveillance for stage I testicular germ cell tumours: results and cost benefit analysis of management options. Eur J Cancer 2000;36:1925–32.6. Sella A., el Naggar A., Ro J.Y. et al. Evidence of malignant features in histologically mature teratoma. J Urol 1991;146:1025–8.Sella A., el Naggar A., Ro J.Y. et al. Evidence of malignant features in histologically mature teratoma. J Urol 1991;146:1025–8.7. Emerson R.E., Ulbright T.M., Zhang S. et al. Nephroblastoma arising in a germ cell tumor of testicular origin. Am J Surg Pathol 2004;28:687–2.Emerson R.E., Ulbright T.M., Zhang S. et al. Nephroblastoma arising in a germ cell tumor of testicular origin. Am J Surg Pathol 2004;28:687–2.8. Mostofi F.K., Price E.B. Tumors of the male genital system. Armed Forces Institute of Pathology. Atlas of tumor pathology, 2nd Series, Fascicle 8, 1973.Mostofi F.K., Price E.B. Tumors of the male genital system. Armed Forces Institute of Pathology. Atlas of tumor pathology, 2nd Series, Fascicle 8, 1973.9. Horwich A., Shipley J., Huddart R. Testicular germ-cell cancer. Lancet 2006; 367;754–65.Horwich A., Shipley J., Huddart R. Testicular germ-cell cancer. Lancet 2006; 367;754–65.10. Rodriguez S., Jafer O., Goker H. et al. Expression profile of genes from 12p intesticular germ cell tumors of adolescents and adults associated with i(12p) and amplification at 12p11.2-p12.1. Oncogene 2003;22;1880–91.Rodriguez S., Jafer O., Goker H. et al. Expression profile of genes from 12p intesticular germ cell tumors of adolescents and adults associated with i(12p) and amplification at 12p11.2-p12.1. Oncogene 2003;22;1880–91.11. Clark A.T., Rodriguez R.T., Bodnar M.S. et al. Human STELLAR, NANOG, and GDF3 genes are expressed in pluripotent cells and map to chromosome 12p13, a hotspot for teratocarcinoma. Stem Cells 2004;22:169–79.Clark A.T., Rodriguez R.T., Bodnar M.S. et al. Human STELLAR, NANOG, and GDF3 genes are expressed in pluripotent cells and map to chromosome 12p13, a hotspot for teratocarcinoma. Stem Cells 2004;22:169–79.12. Oosterhuis J.W., Looijenga L.H. Testicular germ-cell tumours in a broader perspective. Nat Rev Canc 2005;5:210–22.Oosterhuis J.W., Looijenga L.H. Testicular germ-cell tumours in a broader perspective. Nat Rev Canc 2005;5:210–22.13. Gilbert D., Raple E., Shipley J. Testicular germ cell tumours: predisposition genes and the male germ cell niche. Nat Rev Canc 2011;11;278–88.Gilbert D., Raple E., Shipley J. Testicular germ cell tumours: predisposition genes and the male germ cell niche. Nat Rev Canc 2011;11;278–88.14. Skakkebaek N.E., Rajpert-De Meyts E., Main K.M. Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects. Hum Reprod 2001;16:972–8.Skakkebaek N.E., Rajpert-De Meyts E., Main K.M. Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects. Hum Reprod 2001;16:972–8.15. Ohinata Y., Ohta H., Shigeta M. et al. A signaling principle for the specification of the germ cell lineage in mice. Cell 2009;137:571–84.Ohinata Y., Ohta H., Shigeta M. et al. A signaling principle for the specification of the germ cell lineage in mice. Cell 2009;137:571–84.16. Farini D., La Sala G., Tedesco M., De Felici M. Chemoattractant action and molecular signaling pathways of Kit ligand on mouse primordial germ cells. Dev Biol 2007;306:572–83.Farini D., La Sala G., Tedesco M., De Felici M. Chemoattractant action and molecular signaling pathways of Kit ligand on mouse primordial germ cells. Dev Biol 2007;306:572–83.17. Western P. Foetal germ cells: striking the balance between pluripotency and differentiation. Int J Dev Biol 2009;53: 393–409.Western P. Foetal germ cells: striking the balance between pluripotency and differentiation. Int J Dev Biol 2009;53: 393–409.18. Port M., Schmelz H.U., Stockinger M. et al. Gene expression profiling in seminoma and nonseminoma. J Clin Oncol 2005;23:58–69.Port M., Schmelz H.U., Stockinger M. et al. Gene expression profiling in seminoma and nonseminoma. J Clin Oncol 2005;23:58–69.19. Almstrup, K., Hoei-Hansen C.E., Nielsen J.E. et al. Genome-wide gene expression profiling of testicular carcinoma in situ progression into overt tumours. Br J Cancer 2005;92:1934–41.Almstrup, K., Hoei-Hansen C.E., Nielsen J.E. et al. Genome-wide gene expression profiling of testicular carcinoma in situ progression into overt tumours. Br J Cancer 2005;92:1934–41.20. Draper J.S., Smith K., Gokhale P.J. et al. Recurrent gain of chromosomes 17q and 12 in cultured human embryonic stem cells. Nature Biotech 2004;22:53–4.Draper J.S., Smith K., Gokhale P.J. et al. Recurrent gain of chromosomes 17q and 12 in cultured human embryonic stem cells. Nature Biotech 2004;22:53–4.21. Rapley E.A., Turnbull C., Al Olama A.A. et al. A genome-wide association study of testicular germ cell tumor. Nat Genet 2009;41:807–10.Rapley E.A., Turnbull C., Al Olama A.A. et al. A genome-wide association study of testicular germ cell tumor. Nat Genet 2009;41:807–10.22. Rapley E.A., Nathanson K.L. Predisposition alleles for testicular germ cell tumour. Current Opinion in Genetics & Development 2010;20:225–30.Rapley E.A., Nathanson K.L. Predisposition alleles for testicular germ cell tumour. Current Opinion in Genetics & Development 2010;20:225–30.23. Greene M.H., Kratz C.P., Mai P.L. et al. Familial testicular germ cell tumors in adults: 2010 summary of genetic risk factors and clinical phenotype. Endocr-Related Cancer 2010;17:109–21.Greene M.H., Kratz C.P., Mai P.L. et al. Familial testicular germ cell tumors in adults: 2010 summary of genetic risk factors and clinical phenotype. Endocr-Related Cancer 2010;17:109–21.24. van Casteren N.J., Looijenga L.H.J., Dohle G.R. Testicular microlithiasis and carcinoma in situ overview and proposed clinical guideline. Int J Andrology 2009;32:279–87.van Casteren N.J., Looijenga L.H.J., Dohle G.R. Testicular microlithiasis and carcinoma in situ overview and proposed clinical guideline. Int J Andrology 2009;32:279–87.25. Kratz C.P., Mai P.L., Greene M.H. Familial Testicular Germ Cell Tumors. Best Pract Res Clin Endocrinol Metab 2010;24(3):503–13.Kratz C.P., Mai P.L., Greene M.H. Familial Testicular Germ Cell Tumors. Best Pract Res Clin Endocrinol Metab 2010;24(3):503–13.