Обзор посвящен генетическим исследованиям при раке вульвы. В генетических изменениях мутация необратимо меняет нуклеотидную последовательность ДНК, или изменяется количество копий хромосом на клетку. В эпигенетике нуклеотидная последовательность остается неизменной, но активность генов регулируется путем метилирования ДНК или модификации гистонов. Большинство проанализированных исследований посвящены изучению мутаций в гене TP53. Многие исследования указывают на то, что соматические мутации более распространены у ВПЧ-отрицательных, чем у ВПЧ-положительных пациентов. Эпигенетические исследования в основном посвящены гиперметилированию. Наиболее часто изучаемым в эпигенетическом плане является ген CDKN2A. Для большинства изучаемых генов гиперметилирование происходит чаще в плоскоклеточном раке вульвы, чем в предшественниках.
Ключевые слова: рак вульвы, генетика, эпигенетика, вирус папилломы человека.
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The review is devoted to genetic research in cancer of the vulva. In genetic changes, the mutation irreversibly changes the nucleotide sequence of DNA, or the number of copies of chromosomes changes per cell. In epigenetics, the nucleotide sequence remains unchanged, but gene activity is regulated by methylation of DNA or modification of histones. Most of the studies analyzed are devoted to the study of mutations in the TP53 gene. Many studies indicate that somatic mutations are more common in HPV-negative than in HPV-positive patients. Epigenetic studies in the main devoted to hypermethylation. The gene CDKN2A is most often studied in epigenetic terms. For most of the studied genes, hypermethylation occurs more often in squamous cell carcinoma of the vulva than in the precursors.
Key words: vulvar cancer, genetics, epigenetics, human papillomavirus.
1. Stewart BW, Wild C; International Agency for Research on Cancer; World Health Organization. World cancer report 2014. Lyon; Geneva. International Agency for Research on Cancer ; Distributed by WHO Press, 2014. http: //search.ebscohost.com/login.aspx?direct=true&scope=site&db=nlebk&db=nlabk&AN=979458.
2. Gadducci A, Tana R, Barsotti C et al. Crit Rev Oncol Hematol 2012; 83 (1): 71–83.
3. Pino M, Rodriguez-Carunchio L, Ordi J. Histopathology 2013; 62 (1): 161–75.
4. Schuurman MS, van den Einden LC, Massuger LF et al. Eur J Cancer 2013; 49 (18): 3872–80.
5. Van de Nieuwenhof HP, Massuger LF, van der Avoort IA et al. Eur J Cancer 2009; 45 (5): 851–6.
6. Glenn McCluggage W. Pathology 2013; 45 (3): 214–28.
7. Pinto AP, Miron A, Yassin Y et al. Mod Pathol 2010; 23 (3): 404–12.
8. Van der Avoort IA, Shirango H, Hoevenaars BM et al. Int J Gynecol Pathol 2006; 25 (1): 22–9.
9. Rolfe KJ, Eva LJ, MacLean AB et al. Int J Gynecol Cancer 2001; 11 (2): 113–8.
10. Kokka F, Singh N, Faruqi A et al. Int J Gynecol Cancer 2011; 21 (7): 1297–305.
11. Rolfe KJ, MacLean AB, Crow JC et al. British J Cancer 2003; 89 (12): 2249–53.
12. Choschzick M, Hantaredja W, Tennstedt P et al. Int J Gynecol Pathol 2011; 30 (5): 497–504.
13. Raspollini MR, Asirelli G, Moncini D, Taddei GL. Am J Obstet Gynecol 2007; 197 (6): 592.e1–592.e5.
14. Holway AH, Rieger-Christ KM, Miner WR et al. Clin Cancer Res 2000; 6 (8): 3228–35.
15. Soufir N, Queille S, Liboutet M et al. Br J Dermatol 2007; 156 (3): 448–53.
16. Pilotti S, Donghi R, D’Amato L et al. Diagn Mol Pathol 1993; 2 (4): 248–56.
17. Kurvinen K, Tervahauta A, Syrjänen S et al. Anticancer Res 1994; 14 (1A): 177–81.
18. Lee YY, Wilczynski SP, Chumakov A et al. Oncogene 1994; 9 (6): 1655–9.
19. Pilotti S, D’Amato L, Della Torre G et al. Diagn Mol Pathol 1995; 4 (4): 239–48.
20. Milde-Langosch K, Albrecht K, Joram S et al. Int J Cancer 1995; 63 (5): 639–45.
21. Kim Y-T, Thomas NF, Kessis TD et al. Human Pathology 1996; 27 (4): 389–95.
22. Sliutz G, Schmidt W, Tempfer C et al. Gynecol Oncol 1997; 64 (1): 93–8.
23. Ngan HY, Cheung AN, Liu S et al. Eur J Cancer 1999; 35 (3): 481–4.
24. Flowers LC, Wistuba II, Scurry J et al. J Soc Gynecol Investig 1999; 6 (4): 213–21.
25. Marin MC, Jost CA, Brooks LA et al. Nat Genet 2000; 25 (1): 47–54.
26. Brooks LA, Tidy JA, Gusterson B et al. Cancer Res 2000; 60 (24): 6875–7.
27. Wada H, Enomoto T, Yoshino K et al. Am J Clin Pathol 2000; 114 (3): 371–9.
28. O’Nions J, Brooks LA, Sullivan A et al. Br J Cancer 2001; 85 (10): 1551–6.
29. Vanin K, Scurry J, Thorne H et al. J Investig Dermatol 2002; 119 (5): 1027–33.
30. Reddy A, Yuille M, Sullivan A et al. Br J Cancer 2002; 86 (5): 756–60.
31. Gasco M, Sullivan A, Repellin C et al. Oncogene 2002; 21 (12): 1876–81.
32. Chulvis do Val IC, Almeida Filho GL, Valiante PM et al. J Reprod Med 2004; 49 (11): 868–74.
33. Almeida G, do Val I, Gondim C et al. J Reprod Med 2004; 49 (10): 796–9.
34. Osakabe M, Hayashi M, Katayama Y et al. Pathol Int 2007; 57 (6): 322–7.
35. Tapp RA, Feng J, Wesley JJ et al. J Investig Dermatol 2007; 127 (11): 2563–76.
36. Aulmann S, Schleibaum J, Penzel R et al. J Clin Pathol 2008; 61 (9): 1034–7.
37. Gambichler T, Terras S, Kreuter A, Skrygan M. Br J Dermatol 2014; 170 (3): 687–93.
38. Trietsch MD, Spaans VM, ter Haar NT et al. Gynecol Oncol 2014; 135 (1): 149–55.
39. Hay CM, Lachance JA, Lucas FL et al. J Low Genit Tract Dis 2016; 20 (3): 252–6.
40. Qvick A, Sorbe B, Helenius G et al. Med Oncol 2017; 34 (3). http://link.springer.com/10.1007/s12032-017-0893-6
41. Kashofer K, Regauer S. Gynecol Oncol 2017; 146 (2): 314–8.
42. Carrone A, Riganelli L, Savone D et al. Tumori 2017; 103 (6): 511–5.
43. Sznurkowski JJ, Żawrocki A, Biernat W. Oncotarget 2017; 8 (28). http://www.oncotarget.com/fulltext/17581
44. Cao H, Wang S, Zhang Z, Lou J. PLoS ONE 2016; 11 (3): e0152459.
45. Growdon WB, Boisvert SL, Akhavanfard S et al. Gynecol Oncol 2008; 111 (2): 289–97.
46. Lavorato-Rocha AM, Anjos LG, Cunha IW et al. Methods 2015; 77–8: 20–4.
47. Prigge E-S, Urban K, Stiegler S et al. Hum Pathol 2014; 45 (11): 2347–54.
48. Palisoul ML, Mullen MM, Feldman R, Thaker PH. Gynecol Oncol 2017; 146 (2): 305–13.
49. Spaans VM, Trietsch MD, Crobach S et al. PLoS ONE 2014; 9 (3): e93451.
50. Watkins JC, Howitt BE, Horowitz NS et al. Mod Pathol 2017; 30 (3): 448–58.
51. Trietsch MD, Nooij LS, Gaarenstroom KN, van Poelgeest MIE. Gynecol Oncol 2015; 136 (1): 143–57.
52. Bryndorf T, Kirchhoff M, Larsen et al. Cytogenet Genome Res 2004; 106 (1): 43–8.
53. Micci F, Panagopoulos I, Haugom L et al. Genes Chromosomes Cancer 2013; 52 (6): 551–63.
54. Lavorato-Rocha AM, de Melo Maia B, Rodrigues IS et al. Ann Surg Oncol 2013; 20 (1): 31–9.
55. Yangling O, Shulang Z, Rongli C et al. Eur J Gynaecol Oncol 2007; 28 (6): 442–6.
56. Scheistrøen M, Tropé C, Pettersen EO, Nesland JM. Cancer 1999; 85 (5): 1133–8.
57. Worsham MJ, Chen KM, Meduri V et al. Arch Otolaryngol Head Neck Surg 2006; 132 (6): 668.
58. Guerrero D, Guarch R, Ojer A et al. Int J Cancer 2011; 128 (12): 2853–64.
59. Kelemen LE, Köbel M, Chan A et al. Biomed Res Int 2013; 2013: 815894.
60. Oonk MH, Eijsink JJ, Volders HH et al. Gynecol Oncol 2012; 125 (2): 352–7.
61. Lerma E, Esteller M, Herman JG, Prat J. Hum Pathol 2002; 33 (11): 1120–5.
62. Aidé S, Lattario FR, Almeida G et al. J Low Genit Tract Dis 2010; 14 (4): 282–6.
63. Guerrero-Setas D, Pérez-Janices N, Ojer A et al. Histopathology 2013; 63 (5): 659–69.
________________________________________________
1. Stewart BW, Wild C; International Agency for Research on Cancer; World Health Organization. World cancer report 2014. Lyon; Geneva. International Agency for Research on Cancer ; Distributed by WHO Press, 2014. http: //search.ebscohost.com/login.aspx?direct=true&scope=site&db=nlebk&db=nlabk&AN=979458.
2. Gadducci A, Tana R, Barsotti C et al. Crit Rev Oncol Hematol 2012; 83 (1): 71–83.
3. Pino M, Rodriguez-Carunchio L, Ordi J. Histopathology 2013; 62 (1): 161–75.
4. Schuurman MS, van den Einden LC, Massuger LF et al. Eur J Cancer 2013; 49 (18): 3872–80.
5. Van de Nieuwenhof HP, Massuger LF, van der Avoort IA et al. Eur J Cancer 2009; 45 (5): 851–6.
6. Glenn McCluggage W. Pathology 2013; 45 (3): 214–28.
7. Pinto AP, Miron A, Yassin Y et al. Mod Pathol 2010; 23 (3): 404–12.
8. Van der Avoort IA, Shirango H, Hoevenaars BM et al. Int J Gynecol Pathol 2006; 25 (1): 22–9.
9. Rolfe KJ, Eva LJ, MacLean AB et al. Int J Gynecol Cancer 2001; 11 (2): 113–8.
10. Kokka F, Singh N, Faruqi A et al. Int J Gynecol Cancer 2011; 21 (7): 1297–305.
11. Rolfe KJ, MacLean AB, Crow JC et al. British J Cancer 2003; 89 (12): 2249–53.
12. Choschzick M, Hantaredja W, Tennstedt P et al. Int J Gynecol Pathol 2011; 30 (5): 497–504.
13. Raspollini MR, Asirelli G, Moncini D, Taddei GL. Am J Obstet Gynecol 2007; 197 (6): 592.e1–592.e5.
14. Holway AH, Rieger-Christ KM, Miner WR et al. Clin Cancer Res 2000; 6 (8): 3228–35.
15. Soufir N, Queille S, Liboutet M et al. Br J Dermatol 2007; 156 (3): 448–53.
16. Pilotti S, Donghi R, D’Amato L et al. Diagn Mol Pathol 1993; 2 (4): 248–56.
17. Kurvinen K, Tervahauta A, Syrjänen S et al. Anticancer Res 1994; 14 (1A): 177–81.
18. Lee YY, Wilczynski SP, Chumakov A et al. Oncogene 1994; 9 (6): 1655–9.
19. Pilotti S, D’Amato L, Della Torre G et al. Diagn Mol Pathol 1995; 4 (4): 239–48.
20. Milde-Langosch K, Albrecht K, Joram S et al. Int J Cancer 1995; 63 (5): 639–45.
21. Kim Y-T, Thomas NF, Kessis TD et al. Human Pathology 1996; 27 (4): 389–95.
22. Sliutz G, Schmidt W, Tempfer C et al. Gynecol Oncol 1997; 64 (1): 93–8.
23. Ngan HY, Cheung AN, Liu S et al. Eur J Cancer 1999; 35 (3): 481–4.
24. Flowers LC, Wistuba II, Scurry J et al. J Soc Gynecol Investig 1999; 6 (4): 213–21.
25. Marin MC, Jost CA, Brooks LA et al. Nat Genet 2000; 25 (1): 47–54.
26. Brooks LA, Tidy JA, Gusterson B et al. Cancer Res 2000; 60 (24): 6875–7.
27. Wada H, Enomoto T, Yoshino K et al. Am J Clin Pathol 2000; 114 (3): 371–9.
28. O’Nions J, Brooks LA, Sullivan A et al. Br J Cancer 2001; 85 (10): 1551–6.
29. Vanin K, Scurry J, Thorne H et al. J Investig Dermatol 2002; 119 (5): 1027–33.
30. Reddy A, Yuille M, Sullivan A et al. Br J Cancer 2002; 86 (5): 756–60.
31. Gasco M, Sullivan A, Repellin C et al. Oncogene 2002; 21 (12): 1876–81.
32. Chulvis do Val IC, Almeida Filho GL, Valiante PM et al. J Reprod Med 2004; 49 (11): 868–74.
33. Almeida G, do Val I, Gondim C et al. J Reprod Med 2004; 49 (10): 796–9.
34. Osakabe M, Hayashi M, Katayama Y et al. Pathol Int 2007; 57 (6): 322–7.
35. Tapp RA, Feng J, Wesley JJ et al. J Investig Dermatol 2007; 127 (11): 2563–76.
36. Aulmann S, Schleibaum J, Penzel R et al. J Clin Pathol 2008; 61 (9): 1034–7.
37. Gambichler T, Terras S, Kreuter A, Skrygan M. Br J Dermatol 2014; 170 (3): 687–93.
38. Trietsch MD, Spaans VM, ter Haar NT et al. Gynecol Oncol 2014; 135 (1): 149–55.
39. Hay CM, Lachance JA, Lucas FL et al. J Low Genit Tract Dis 2016; 20 (3): 252–6.
40. Qvick A, Sorbe B, Helenius G et al. Med Oncol 2017; 34 (3). http://link.springer.com/10.1007/s12032-017-0893-6
41. Kashofer K, Regauer S. Gynecol Oncol 2017; 146 (2): 314–8.
42. Carrone A, Riganelli L, Savone D et al. Tumori 2017; 103 (6): 511–5.
43. Sznurkowski JJ, Żawrocki A, Biernat W. Oncotarget 2017; 8 (28). http://www.oncotarget.com/fulltext/17581
44. Cao H, Wang S, Zhang Z, Lou J. PLoS ONE 2016; 11 (3): e0152459.
45. Growdon WB, Boisvert SL, Akhavanfard S et al. Gynecol Oncol 2008; 111 (2): 289–97.
46. Lavorato-Rocha AM, Anjos LG, Cunha IW et al. Methods 2015; 77–8: 20–4.
47. Prigge E-S, Urban K, Stiegler S et al. Hum Pathol 2014; 45 (11): 2347–54.
48. Palisoul ML, Mullen MM, Feldman R, Thaker PH. Gynecol Oncol 2017; 146 (2): 305–13.
49. Spaans VM, Trietsch MD, Crobach S et al. PLoS ONE 2014; 9 (3): e93451.
50. Watkins JC, Howitt BE, Horowitz NS et al. Mod Pathol 2017; 30 (3): 448–58.
51. Trietsch MD, Nooij LS, Gaarenstroom KN, van Poelgeest MIE. Gynecol Oncol 2015; 136 (1): 143–57.
52. Bryndorf T, Kirchhoff M, Larsen et al. Cytogenet Genome Res 2004; 106 (1): 43–8.
53. Micci F, Panagopoulos I, Haugom L et al. Genes Chromosomes Cancer 2013; 52 (6): 551–63.
54. Lavorato-Rocha AM, de Melo Maia B, Rodrigues IS et al. Ann Surg Oncol 2013; 20 (1): 31–9.
55. Yangling O, Shulang Z, Rongli C et al. Eur J Gynaecol Oncol 2007; 28 (6): 442–6.
56. Scheistrøen M, Tropé C, Pettersen EO, Nesland JM. Cancer 1999; 85 (5): 1133–8.
57. Worsham MJ, Chen KM, Meduri V et al. Arch Otolaryngol Head Neck Surg 2006; 132 (6): 668.
58. Guerrero D, Guarch R, Ojer A et al. Int J Cancer 2011; 128 (12): 2853–64.
59. Kelemen LE, Köbel M, Chan A et al. Biomed Res Int 2013; 2013: 815894.
60. Oonk MH, Eijsink JJ, Volders HH et al. Gynecol Oncol 2012; 125 (2): 352–7.
61. Lerma E, Esteller M, Herman JG, Prat J. Hum Pathol 2002; 33 (11): 1120–5.
62. Aidé S, Lattario FR, Almeida G et al. J Low Genit Tract Dis 2010; 14 (4): 282–6.
63. Guerrero-Setas D, Pérez-Janices N, Ojer A et al. Histopathology 2013; 63 (5): 659–69.
1. ФГБУН «Центр теоретических проблем физико-химической фармакологии» РАН. 119991, Россия, Москва, Ленинский пр-т, д. 38а, корп. 1;
2. ФГБНУ «НИИ вакцин и сывороток им. И.И.Мечникова». 105064, Россия, Москва, Малый Казенный пер., д. 5а;
3. ГБУЗ «Московский научно-практический центр дерматовенерологии и косметологии» Департамента здравоохранения г. Москвы. 119071, Россия, Москва, Ленинский пр-т, д. 17
*marykor@bk.ru
1. Center for Theoretical Problems of Physicochemical Pharmacology of the Russian Academy of Sciences. 119991, Russian Federation, Moscow, Leninskiy pr-t, d. 38a, korp. 1;
2. I.I.Mechnikov Research Institute of Vaccines and Sera. 105064, Russian Federation, Moscow, Malyi Kazennyi per., d. 5a;
3. Moscow Scientific and Practical Center of Dermatology and Venereology and Cosmetology of the Department of Health of Moscow. 119071, Russian Federation, Moscow, Leninskiy pr-t, d. 17
*marykor@bk.ru