Анализ молекулярно-генетичеcких нарушений хромосомы 6, ассоциированных с прогрессией рака шейки матки
![Диссертация: Анализ молекулярно-генетичеcких нарушений хромосомы 6, ассоциированных с прогрессией рака шейки матки](https://westud.ru/work/2744369/cover.png)
Диссертация
Установлено, что потенциальной мишенью аллельных делеций микросателлитного маркера D6S273, является новый ген LY6G6D, расположенный в районе генов HLA III класса (6р21.3). Делеции маркера D6S273 выявлены на ранних стадиях канцерогенеза шейки матки в CIN. Впервые предложена экзон-интронная структура гена LY6G6D, которая объединяет два гена G6D и G6 °F в один, при этом микросателлит D6S273… Читать ещё >
Содержание
- Список сокращений
- Глава 1. Обзор литературы
- 1. 1. Вирус папиллом человека — этиологический фактор рака шейки матки
- 1. 1. 1. Инфекция шейки матки вирусом папиллом человека
- 1. 1. 2. Функции онкогенов HPV
- 1. 2. Исследование генетических нарушений при раке шейки матки
- 1. 2. 1. Генетические нарушения на хромосоме 3 в CIN и РШМ
- 1. 2. 2. Генетические нарушения на хромосоме 6 в CIN и РШМ
- 1. 2. 3. Молекулярно-генетические маркеры некоторых важных свойств опухоли
- 1. 3. Генетическая гетерогенность CIN и рака шейки матки 29 1.3.1. Исследование генетической гетерогенности CIN и рака шейки матки
- 1. 1. Вирус папиллом человека — этиологический фактор рака шейки матки
- Заключение
- Глава 2. Материалы и методы 34 2.1. Клинические материалы и характеристика, полученной ДНК 34 2.2 Метод анализа потери гетерозиготности
- 2. 2. 1. Амплификация ДНК
- 2. 2. 2. Электрофоретическое разделение продуктов амплификации в денатурирующем полиакриламидном геле 38 2.2.3. Методы визуализации продуктов ПЦР, разделенных в полиакриламидном геле
- 2. 3. Метод анализа инактивации Х-хромосомы
- 2. 4. Компьютерный анализ нуклеотидной последовательности фрагментов хромосомы 6, содержащих микросателлитные маркеры D6S273 и D6S
- 2. 5. Обратная транскрипция РНК из нормальной ткани и РШМ
- Список использованных растворов
- Глава 3. Результаты собственных исследований
- 3. 1. Анализ потери гетерозиготности на хромосоме 6 в
- ДНК из микродиссецированных образцов РШМ и CIN
- 3. 2. Изучение гетерогенности РШМ
- 3. 2. 1. Исследование гетерогенности РШМ методом анализа
- X. — хромосомной инактивации
- 3. 2. 2. Анализ гетерогенности в образце N3 рака шейки матки
- 3. 2. 3. Анализ генетической гетерогенности рака шейки матки в двух синхронных фокусах образца РШМ №
- 3. 4. Изучение гена LY6G6D 63 3.4.1. Гены-мишени аллельных делеций 63 3.4.2 Результаты анализа in silico структуры гена G6D
- 3. 4. 3. Экзон-интронная структура гена LY6G6D
- 3. 4. 4. Трансляция in silico основных транскриптов гена LY6G6D
- 3. 4. 5. Определение границ первого и последнего экзонов гена LY6G6D
- 3. 4. 6. Структура гена LY6G6D, транскрипты и белковые продукты
- 3. 4. 7. Уточнение экзон-интронной структуры гена LY6G6E
- 3. 4. 8. Анализ экзон-интроппой структуры гена LY6G6D методом ОТ-ПЦР
- 3. 4. 8. 1. Анализ экспрессии гена LY6G6D в опухолевых клеточных линиях
- 3. 4. 8. 2. Определение пограничной З'-последовательности транскрипта G6D гена LY6G6D
- 3. 4. 8. 3. Результат определения пограничной 5'-последовательности транскрипта G6D гена LY6G6D
- 3. 4. 9. Сплайсинг мРНК гена LY6G6D. Сплайсинг транскрипта G6D 80 3.4.9.1. Анализ экспрессии гена LY6G6D в РНК из крови доноров
- 3. 4. 10. Поиск мутаций, влияющих на сплайсинг LY6G6D
- 3. 4. 11. Транслокация в гене LY6G6D
- 3. 5. Ген LOC
- 3. 5. 1. Экзон-интронная структура гена LOC
- 3. 5. 2. Положение гена LOC57107 на генной карте
- 3. 5. 3. Варианты альтернативного сплайсинга гена LOC
- 3. 5. 4. Трансляция in silico некоторых мРНК LOC
- 3. 5. 5. Результат анализа экспрессии гена LOC57107 методом ОТ-ПЦР в образцах нормальной и опухолевой ткани шейки матки и некоторых опухолевых клеточных линиях
Список литературы
- Holland, Frei, Cancer Medcine 6, ВС Decker Inc Hamilton, London, 2003.
- Киселев Ф.Л., Мазуренко H.H., Киселева Н. П., Кобзева В. К., Семенова JI.A., Павлова
- JI.C., Беляков И. С., Блиев А. Ю., Ешелев Э. М., Иванова Т. А., Петренко А. А. Молекулярные маркеры рака шейки матки. //Вестник РАМН. 2002. Т.1. С.8−14.
- Мазуренко Н.Н., Беляков И. С., Блиев А.Ю, Гуо Ж., Ху К., Винокурова С. В., Павлова J1.C.,
- Понтен Я., Киселев Ф. Л. Генетические изменения па хромосоме 6, ассоциированные с прогрессией рака шейки матки. //Молекулярная биология. 2003. Т.38. С.472−481.
- Мазуренко Н.Н., Блиев А. Ю., Биджиева Б. А., Песков Д. С., Снигур Н. В., Савинова Е.Б.,
- Киселев Ф.Л. Генетические изменения на хромосоме 6, ассоциированные с прогрессией рака шейки матки. Молекулярная биология. 2006. Т.40. С. 1−12.
- Малюкова А. В., В. И. Логинов, Д. С. Ходырев, Е. Л. Хадырова, И. В. Пронина, Т. А.
- Иванова, Ф. Л. Киселев, Е. Р. Забаровский, Н. П. Киселева, Э. А. Брага Метилирование предполагаемого гена-супрессора RASSF1A в опухолях шейки матки //Молекулярная биология. 2004.Т.38. С.1005−1013.
- И. С. Беляков, Т. А. Каракашева, Н. Н. Мазуренко. Экзон-интроиная структура гена1.6G6D. //Молекулярная биология. 2009. Т.43. С.590−598
- В.А.Журбицкая, Л. И. Федорова, Н. МЛрцева, Л. В. Савельева, А. В. Зеленин, Ф. Л. Киселев.
- Трансформация иммортализованных эмбриональных фибробластов крысы геном Е7 вируса папилломы человека типа 16. //Молекулярная биология. 1999. Т.ЗЗ. С.282−287.
- Acevedo С.М., Henriquez М., Emmert-Buck M.R., Chuaqui R.F. Loss of heterozygosity onchromosome arms 3p and 6q in microdissected adenocarcinomas of the uterine cervix and adenocarcinoma in situ. //Cancer. 2002. Vol.94. P.793−802.
- Adams M.D., Soares M.B., Kerlavage A.R., Fields C., Venter J.C. Rapid cDNA sequencingexpressed sequence tags) from a directionally cloned human infant brain cDNA library. //Nat Genet. 1993. Vol.4. P.373−80.
- Allen D.G., White D.J., Hutchins A.M., Scurry J.P., Tabrizi S.N., Garland S.M., Armes J.E. Progressive genetic aberrations detected by comparative genomic hybridization in squamous cell cervical cancer. //Br J Cancer. 2000. Vol.83. P. 1659−63.
- Altschul S.F., Gish W., Miller W., Myers E.W. & Lipman D.J. Basic local alignment search tool. //J. Mol. Biol. 1990. Vol.215. P.403−410.
- Altschul S.F., Madden T.L., Schaffer A. A., Zhang J., Zhang Zh., Miller W. and Lipman D.J. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs //Nucleic Acids Research. 1997. Vol.25. P.3389−3402
- Arends M.J., Buckley C.H., Wells M. Aetiology, pathogenesis, and pathology of cervical neoplasia. //J Clin Pathol. 1998 Vol.51 P.96−103.
- Atkin N. B, Baker M.C. Small metacentric marker chromosomes in unbanded archival material from carcinomas of the cervix uteri.//Cytobios. 1991. Vol.65. P. 179−85.
- Atkin N.B., Baker M.C., Fox M.F. Chromosome changes in 43 carcinomas of the cervix uteri.//Cancer Genet Cytogenet. 1990. Vol.44 P.229−41.
- Atkin N.B., Baker M.C. DNA ploidy of cervical intraepithelial neoplasia (CIN). //Cancer Genet Cytogenet. 1997 Vol.94. P.151−2.
- Backsch C., Wagenbach N., Nonn M, Leistritz S., Stanbridge E., Schneider A., Durst M. Microcell-mediated transfer of chromosome 4 into HeLa cells suppresses telomerase activity. //Genes Chromosomes Cancer. 2001. Vol.31. P. 196−8.
- Banga S.S., Kim S., Hubbard K., Dasgupta T., Jha K.K., Patsalis P., Hauptschein R., Gamberi B., Dalla-Favera R., Kraemer P., Ozer H.L. SEN6, a locus for SV40-mediated immortalization of human cells, maps to 6q26−27. //Oncogene. 1997. Vol.14. P.313−21.
- Bellanger S., Blachon S., Mechali F., Bonne-Andrea C., Thierry F. High-risk but not low-risk HPV E2 proteins bind to the APC activators Cdhl and Cdc20 and cause genomic instability. //Cell Cycle. 2005. Vol.4. P.1608−15.
- Belyakov I., Mazurenko N. Identification of two loci of frequent allelic deletions on chromosome 6 involved in cervical cancer progression. // Proceedings book of ECCO conference, Copenhagen 2003, Eur. J. of Cancer, Suppl. Vl, N5, P. S181
- Bernard H.U. Gene expression of genital human papillomaviruses and considerations on potential antiviral approaches. //Antivir Ther. 2002. Vol.7. P.219−37.
- Bernat A., Awakumov N., Mymryk J.S., Banks L. Interaction between the HPV E7 oncoprotein and the transcriptional coactivator p300. //Oncogene. 2003. Vol.22. P.7871−81.
- Boshart M., Gissmann L., Ikenberg H., Kleinheinz A., Scheurlen W., zur Hauscn H. A new type of papillomavirus DNA, its presence in genital cancer biopsies and in cell lines derived from cervical cancer. //EMBO J. 1984. Vol.3. P. 1151−7.
- Bravaccini S., Sanchini M.A., Amadori A., Medri L., Saragoni L., Calistri D., Monti F., Volpi A., Amadori D. Potential of telomerase expression and activity in cervical specimens as a diagnostic tool. //J Clin Pathol. 2005 Sep-58(9):911−4.
- Brehm A., Nielsen S.J., Miska E.A., McCance D.J., Reid J.L., Bannister A.J., Kouzarides T.
- The E7 oncoprotein associates with Mi2 and histone deacetylase activity to promote cell growth. //EMBO J. 1999. Vol.18. P.2449−58.
- Brinton L.A., Reeves W.C., Brenes M.M., et al. Parity as a risk factor for cervical cancer. //American Journal of Epidemiology. 1989. Vol.130. P.486−496.
- Burk R. D, Ho G.Y., Beardsley L., Lempa M., Peters M., Bierman R. Sexual behavior and partner characteristics are the predominant risk factors for genital human papillomavirus infection in young women. //J Infect Dis. 1996. Vol.174. P.679−89.
- Butler D., Collins C., Mabruk M., Leader M.B., Kay E.W. Loss of Fhit expression as a potential marker of malignant progression in preinvasive squamous cervical cancer.//Gynecol Oncol. 2002. Vol.86.-P. 144−9.
- Calvanese V., Mallya M., Campbell R.D., Aguado B. Regulation of expression of two LY-6 family genes by intron retention and transcription induced chimerism. //BMC Mol Biol. 2008. Vol.25. P.81−97.
- Chu T.Y., Shen C.Y., Chiou Y.S., Lu J.J., Perng C.L., Yu M.S., Liu H.S. HPV-associated cervical cancers show frequent allelic loss at 3pl4 but no apparent aberration of FHIT mRNA. //Int J Cancer. 1998. Vol.75. P. 199−204.
- Chuaqui R., Silva M., Emmert-Buck M. Allelic deletion mapping on chromosome 6q and X chromosome inactivation clonality patterns in cervical intraepithelial neoplasia and invasive carcinoma.//Gynecol Oncol. 2001. Vol.80. P.364−71.
- Chung G.T., Huang D.P., Lo K.W., Chan M.K., Wong F.W. Genetic lesion in the carcinogenesis of cervical cancer.//Anticancer Res. 1992. Vol.12. P.1485−90.
- Chung T.K., Cheung T.H., Lo W.K., Yu M.Y., Hampton G.M., Wong H.K., Wong Y.F. Loss of heterozygosity at the short arm of chromosome 3 in microdissected cervical intraepithelial neoplasia. //Cancer Lett. 2000. Vol.154. P. 189−94.
- Comprehensive cervical cancer control: a guide to essential practice. WHO Library Cataloguing-in-Publication Data. World Health Organization 2006 WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland.
- Cottage A., Dowen S., Roberts I., Pett M., Coleman N., Stanley M. Early genetic events in HPV immortalised keratinocytes. //Genes Chromosomes Cancer. 2001. Vol.30. P.72−9.
- Dal Maso L., Polesel J., Serraino D., et al. Pattern of cancer risk in persons with AIDS in Italy in the HAART era. //Br J Cancer. 2009. Vol.100. P.840−7.
- Dasgupta S., Chakraborty S.B., Roy A., Roychowdhury S., Panda C.K. Differential deletions of chromosome 3p are associated with the development of uterine cervical carcinoma in Indian patients. //Mol Pathol. 2003. Vol.56. P.263−9.
- De Vet E.C., Aguado B., Campbell R.D. Adaptor signalling proteins Grb2 and Grb7 are recruited by human G6f, a novel member of the immunoglobulin superfamily encoded in the MHC. //Biochem J. 2003. Vol.375. P.207−13.
- Delias A., Torhorst J., Schultheiss E., Mihatsch M.J., Moch H. DNA sequence losses on chromosomes lip and 18q are associated with clinical outcome in lymph node-negative ductal breast cancer. //Clin Cancer Res. 2002. Vol.8. P. 1210−6.
- Donalisio M., Cornaglia M., Landolfo S., Lembo D. TGF-betal and IL-4 downregulate human papillomavirus-16 oncogene expression but have differential effects on the malignant phenotype of cervical carcinoma cells.//Virus Res. 2008. Vol.132. P.253−6.
- Duensing S., Munger K. Human papillomavirus type 16 E7 oncoprotein can induce abnormal centrosome duplication through a mechanism independent of inactivation of retinoblastoma protein family members. //J Virol. 2003. Vol. 77. P.12 331−5.
- Duensing S., Munger K. Human papillomaviruses and centrosome duplication errors: modeling the origins of genomic instability. //Oncogene. 2002. Vol.21. P.6241−8.
- Durst M., Gissmann L., Ikenberg H., zur Hausen H. A papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions. //Proc Natl Acad Sci U S A. 1983. Vol.80. P.3812−5.
- Doorbar J. Molecular biology of human papillomavirus infection and cervical cancer. //Clin Sci (Lond) 2006. Vol.110. P.525−41.
- Eder C., Chaganti R.S., Murty V.V., Greskotter K.R., Giesing M. Laser microdissection and molecular typing of dysplastic cells from Pap smears: a new approach to early detection of cervical cancer. //Pathologe. 2004. Vol.25. P.209−16.
- ELhamidi A., Hamoudi R.A., Kocjan G., Du M.Q. Cervical intraepithelial neoplasia: prognosis by combined LOH analysis of multiple loci. //Gynecol Oncol. 2004. Vol.94. P.671−9.
- Evans MF, Koreth J, Bakkenist CJ, Herrington CS, McGee JO. Allelic deletion at Ilq23.3-q25 is an early event in cervical neoplasia. //Oncogene. 1998. Vol.16. P.2557−64.
- Ferreira R, Naguibneva I, Mathieu M, Ait-Si-Ali S, Robin P, Pritchard LL, Harel-Bellan A.
- Cell cycle-dependent recruitment of HDAC-1 correlates with deacetylation of histone Il4 on an Rb-E2 °F target promoter. //EMBO Rep. 2001. Vol.2. P.794−9.
- Frohman M.A., Dush M.K., Martin G.R. Rapid production of full-length cDNAs from rare transcripts: amplification using a single gene-specific oligonucleotide primer. //Proc. Natl. Acad. Sci. USA. 1988. Vol.85. P.8998−9002.
- Fouret P.J., Dabit D., Mergui J.L., Uzan S. Loss of heterozygosity on the short arm of chromosome 3 in cervical intra-epithelial neoplasia without concomitant cervical carcinoma. //Pathobiology. 1998. Vol.66. P.306−10.
- Fu X.S., Choi E., Bubley G.J., Balk S.P. Identification of hypoxia-inducible factor-lalpha (HIF-1 alpha) polymorphism as a mutation in prostate cancer that prevents normoxia-induced degradation. //Prostate. 2005. Vol.63. P.215−221.
- Gyapay G, Morissette J, Yignal A, Dib C, Fizames C, Millasseau P, Marc S, Bernardi G, Lathrop M, Weissenbach J. The 1993−94 Genethon human genetic linkage map. //Nat Genet. 1994. Vol.7. P.246−339.
- Gish, W. & States, D.J. Identification of protein coding regions by database similarity search. //Nature Genet. 1993. Vol.3. P.266−272.
- Gissmann L., Pfister H., and zur Hausen H. Human papilloma viruses (HPV): characterization of four different isolates. //Virology. 1977. Vol.76. P.569−580.
- Gissmann L., zur Hausen H. Partial characterization of viral DNA from human genital warts (Condylomata acuminata). //Int J Cancer. 1980. Vol.25. P.605−9.
- Gonzalez-Sancho J.M., Garcia V., Bonilla F., Munoz A. Thyroid hormone receptors/THR genes in human cancer. Cancer Lett. 2003. Vol.192. P.121−32.
- Gostout B.S., Poland G.A., Calhoun E.S., Sohni Y.R., Giuntoli R.L. 2nd, McGovern R.M., Sloan J.A., Cha S.S., Persing D.H. Gynecol Oncol. 2003. Vol.88. P.326−32. TAP1, TAP2, and FILA-DR2 alleles are predictors of cervical cancer risk.
- Guo X., Deng Y., Lin Y., Cosme-Blanco W., Chan S., He H., Yuan G., Brown E.J., Chang S. Dysfunctional telomeres activate an ATM-ATR-dependent DNA damage response to suppress tumorigenesis. //EMBO J. 2007. Vol.26. P.4709−19.
- Guo Z., Hu X., Afink G., Ponten F., Wilander E., Ponten J. Comparison of chromosome 3p deletions between cervical precancers synchronous with and without invasive cancer. //Int J Cancer. 2000. Vol.86. P.518−23.
- Harris A.L. Hypoxia a key regulatory factor in tumor growth. //Nat. Rev. Cancer 2002. Vol.2. P.3847.
- Hausen H.Z. Papillomaviruses—to vaccination and beyond. //Biochemistry (Mosc). 2008. Vol.73. P.498−503.
- Hawley-Nelson P, Vousden KH, Hubbert NL, Lowy DR, Schiller JT. HPV 16 E6 and E7 proteins cooperate to immortalize human foreskin keratinocytes. //EMBO J. 1989. Vo.8. P.3905−10.
- Herbig U., Jobling W.A., Chen B.P., Chen D.J., Sedivy J.M. Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21(CIPl), but not pl6(INK4a).//Mol Cell. 2004. Vol.14. P.501−13.
- Herzog CR, Crist KA, Sabourin CL, Kelloff GJ, Boone CW, Stoner GD, You M. Mol Carcinog. 2001 Mar-30(3): 159−68. Chromosome 3p tumor-suppressor gene alterations in cervical carcinomas.
- Heselmeyer K., Macville M., Schrock E., Blegen H., Hellstrom A.C., Shah K., Auer G., Ried T.
- Advanced-stage cervical carcinomas are defined by a recurrent pattern of chromosomal aberrations revealing high genetic instability and a consistent gain of chromosome arm 3q. Genes Chromosomes Cancer. 1997. Vol.19. P.233−40.
- Hirschfeld M., zur Hausen A., Bettendorf H., Jiiger M., Stickeler E. Alternative splicing of Cyr61 is regulated by hypoxia and significantly changed in breast cancer. //Cancer Res. 2009. Vol.69. P.2082−90.
- Hui J., Hung L.H., Heiner M., Schreiner S., Neumuller N., Reither G., Haas S.A., Bindereif A. Intronic CA-repeat and CA-rich elements: a new class of regulators of mammalian alternative splicing. //EMBO J. 2005. Vol.24. P. 1988−98.
- Iftner T., Elbel M., Schopp B., Hiller T., Loizou J.I., Caldecott K.W., Stubenrauch F. Interference of papillomavirus E6 protein with single-strand break repair by interaction with XRCC1. //EMBO J. 2002. Vol.21. P.4741−8.
- Jackson S., Harwood C., Thomas M., Banks L. & Storey A. Role of Bak in UV-induced apoptosis in skin cancer and abrogation by HPV E6 proteins. //Genes Dev. 2000. Vol. 14. P.3065−3073.
- Kabsch K., Mossadegh N., Kohl A., Komposch G., Schenkel J., Alonso A., Tomakidi P. The HPV-16 E5 protein inhibits TRAIL- and FasL-mediated apoptosis in human keratinocyte raft cultures. //Intervirology. 2004. Vol.47. P.48−56.
- Karlsen F., Rabbitts P.H., Sundresan V., Hagmar B. PCR-RFLP studies on chromosome 3p in formaldehyde-fixed, paraffin-embedded cervical cancer tissues. //Int J Cancer. 1994. Vol.58. P.787−92.
- Kersemaekers A.M., van de Vijver M.J., Kenter G.G., Fleuren G.J. Genetic alterations during the progression of squamous cell carcinomas of the uterine cervix. //Genes Chromosomes Cancer. 1999. Vol.26. P.346−54.
- Kersemaekers A.M., Hermans J., Fleuren G.J., van de Vijver MJ. Loss of heterozygosity for defined regions on chromosomes 3, 11 and 17 in carcinomas of the uterine cervix. //Br J Cancer. 1998. Vol.77. P.192−200.
- Kim, W.Y., Kaelin, W.G. Role of VHL gene mutation in human cancer. //J. Clin. Oncol. 2004. Vol.22. P.4991−5004.
- Kimura K., Wakamatsu A., Suzuki Y. et al. Diversification of transcriptional mcidulation: large-scale identification and characterization of putative alternative promoters of human genes. //Genome Res. 2006. Vol.16. P.55−65.
- Klingelhutz A.J., Foster S.A., McDougall J.K. Telomerase activation by the E6 gene product of human papillomavirus type 16. //Nature. 1996. Vol.380. P.79−82.
- Kloth J.N., Kenter G.G., Spijker H.S., Uljee S., Corver W.E., Jordanova E.S., Fleuren G.J., Gorter A. Expression of Smad2 and Smad4 in cervical cancer: absent nuclear Smad4 expression correlates with poor survival. //Mod Pathol. 2008. Apr 18.
- Knudson AG. Two genetic hits (more or less) to cancer. //Nat Rev Cancer. 2001. Vol.1. P. 157−62.
- Kohno T, Takayama H, Hamaguchi M, Takano H, Yamaguchi N, Tsuda H, Hirohashi S, Vissing PI, Shimizu M, Oshimura M, et al. Deletion mapping of chromosome 3p in human uterine cervical cancer. //Oncogene. 1993. Vol.8. P.1825−32.
- Koopman L. A, Corver W.E., van der Slik A.R., Giphart M.J., Fleuren G.J. Multiple genetic alterations cause frequent and heterogeneous human histocompatibility leukocyte antigen class I loss in cervical cancer. //J. Exp. Med. 2000. Vol.191. P.961−975.
- Kudo K., Sato S., Yokoyama Y., Fukushi Y., Maruyama H., Saito Y. Clinical significance of numerical aberrations on chromosome 17 in uterine cervical and endometrial neoplasias. //Eur J Gynaecol Oncol. 2000. Vol.21. P.491−3.
- Kurose K., Zhou X.P., Araki T., Eng C. Biallelic inactivating mutations and an occult germline mutation of PTEN in primary cervical carcinomas. //Genes Chromosomes Cancer. 2000. Vol.29. P. 166−72.
- Lam E.W., Morris J.D., Davies R., Crook T., Watson R.J., Vousden K.FI. HPV16 E7 oncoprotein deregulates B-myb expression: correlation with targeting of pl07/E2 °F complexes. //EMBO J. 1994. Vol.13. P.871−8.
- Larson AA, Liao SY, Stanbridge EJ, Cavenee WK, Hampton GM. Cancer Res. 1997 Oct l-57(19):4171−6. Genetic alterations accumulate during cervical tumorigenesis and indicate a common origin for multifocal lesions.
- Lee SH, Lee SH. Aberrant FHIT transcripts in human colorectal cancers. //Res Commun Mol Pathol Pharmacol. 2005. Vol.117−118. P.153−65.
- Leechanachai P, Banks L, Moreau F, Matlashewski G. The E5 gene from human papillomavirus type 16 is an oncogene which enhances growth factor-mediated signal transduction to the nucleus. //Oncogene. 1992. Vol.7. P.19−25.
- Po-Huang Liang, Tzu-Ping Ko and Andrew H.-J. Wang Structure, mechanism and function of prenyltransferases Eur.J.Biochem. 269, 3339−3354 (2002).
- MacLachlan T.K., Dash B.C., Dicker D.T., El-Deiry W.S. Repression of BRCA1 through a feedback loop involving p53. //J Biol Chem. 2000. Vol.275. P.31 869−75.
- Mallya M., Campbell R.D. and Aguado B. Transcriptional analysis of a novel cluster of LY-6 family members in the human and mouse major histocompatibility complex: five genes with many splice forms. //Genomics 2002. Vol.80. P. l 13−123.
- Matsuse M., Saenko V., Sedliarou I., Rogounovitch T., Nakazawa Y., Mitsutake N., Akulevich N., Namba H., Yamashita S. A novel role for thyroid hormone receptor beta in cellular radiosensitivity. //J Radiat Res (Tokyo). 2008. Vol.49. P. 17−27.
- Mark H.F., Feldman D., Samy M., Sun C., Das S., Mark S., Lathrop. Assessment of chromosome 8 copy number in cervical cancer by fluorescent in situ hybridization.//J. Exp Mol Pathol. 1999. Vol.66. P. 157−62.
- Markowska J., Grabowski J.P., Tomaszewska K., Kojs Z., Pudelek J., Skrzypczak M., Sobotkowski J., Emerich J., Olejek A., Filas V. Significance of hypoxia in uterine cervical cancer. Multicentre study. //Eur J Gynaecol Oncol. 2007. Vol.28. P.386−8.
- Mazurenko N.N., Beliakov I.S., Bliev A.Iu., Guo Z., Hu X., Vinokurova S.V., Bidzhieva B.A., Pavlova L.S., Ponten J., Kiselev F.L. Cervical carcinoma progression-associated genetic alterations on chromosome 6. //Mol Biol (Mosk). 2003. Vol.37. P.472−81.
- Mazurenko N., Attaleb M., Gritsko T., Semjonova L., Pavlova L., Sakharova O., Kisseljov F.
- High resolution mapping of chromosome 6 deletions in cervical cancer. //Oncol Rep. 1999. Vol.6. P.859−63.
- Mitra A.B., Murty V.V., Singh V., Li R.G., Pratap M., Sodhani P., Luthra U.K., Chaganti R.S. Genetic alterations at 5pl5: a potential marker for progression of precancerous lesions of the uterine cervix. //J Natl Cancer Inst. 1995. Vol.87. P.742−5.
- Mitra A.B., Murty V.V., Li R.G., Pratap M., Luthra U.K., Chaganti R.S. Allelotype analysis of cervical carcinoma. //Cancer Res. 1994. Vol.54. P.4481−7.
- Miyai K., Furugen Y., Matsumoto T., Iwabuchi K., Hirose S., Kinoshita K., Fujii PI. Loss of heterozygosity analysis in uterine cervical adenocarcinoma. //Gynecol Oncol. 2004. Vol.94. P. 115−20.
- Moore D.H. Cervical cancer. //Obstet Gynecol. 2006. Vol.107. P.1152−61.
- Mullokandov M.R., Kholodilov N.G., Atkin NB., Burk R.D., Johnson A.B., Klinger H.P. Genomic alterations in cervical carcinoma: losses of chromosome heterozygosity and human papilloma virus tumor status. //Cancer Res. 1996. Vol.56. P. 197−205.
- Mungall A.J., Palmer S.A., Sims S.K., et al. The DNA sequence and analysis of human chromosome 6. //Nature. 2003. Vol.425. P.805−11.
- Munger K., Werness B.A., Dyson N., Phelps W.C., Harlow E., Howley P.M. Complex formation of human papillomavirus E7 proteins with the retinoblastoma tumor suppressor gene product. //EMBO J. 1989. Vol.8. P.4099−105.
- Munoz N., Franceschi S., Bosetti C. et al. Role of parity and human papillomavirus in cervical cancer: the IARC multicentric case-control study. //Lancet. 2002. Vol.359. P.1093−1101.
- Murty V.V., Mitra A.B., Das B.C., Murthy N.S., Luthra U.K. Chromosomal phenotypes in patients with precancerous lesions of the uterine cervix progressed to cancer during follow-up. //Oncology. 1988. Vol.45. P.384−8.
- Nakamura M., Bodily J.M., Beglin M., Kyo S., Inoue M., Laimins L.A. Hypoxia-specific stabilization of HIF-lalpha by human papillomaviruses. //Virology. 2009. Mar 23.
- Neto D., Garcia Correa R., Verjovski-Almeida S., et al. Shotgun sequencing of the human transcriptome with ORF expressed sequence tags. //Proc. Natl. Acad. Sci. USA. 2000. Vol. 97. P.3491−3496.
- O’sullivan M.J., Rader J.S., Gerhard D.S., Li Y., Trinkaus K.M., Gersell D.J., Huettner P.C. Loss of heterozygosity at llq23.3 in vasculoinvasive and metastatic squamous cell carcinoma of the cervix. //Hum Pathol. 2001. Vol.32. P.475−8.
- Oh S.T., Kyo S., Laimins L.A. Telomerase activation by human papillomavirus type 16 E6 protein: induction of human telomerase reverse transcriptase expression through Myc and GC-rich Spl binding sites. //J Virol. 2001. Vol.75. P.5559−66.
- Olaharski A.J., Sotelo R., Solorza-Luna G., Gonsebatt M.E., Guzman P., Mohar A., Eastmond D.A. Tetraploidy and chromosomal instability are early events during cervical carcinogenesis. Carcinogenesis. 2006. Vol.27. P.337−43.
- Oliveira A.M., Fletcher J. A. Translocation breakpoints in cancer //Encyclopedia of the human genome. 2003. Macmillan Publishers Ltd, Nature Publishing Group (www.ehgonline.net).
- Orange J.S., Fassett M.S., Koopman L.A., Boyson J.E., Strominger J.L. Viral evasion of natural killer cells. //Nat Immunol. 2002. Vol.3. P.1006−12.
- Orth G., Favre M., and Croissant O. Characterization of a new type of human papillomavirus that causes skin warts. //J. Virol. 1977. Vol.24. P.108−120.
- Pan H., Griep A.E. Altered cell cycle regulation in the lens of HPV-16 E6 or E7 transgenic mice: implications for tumor suppressor gene function in development. //Genes Dev. 1994. Vol.8. P.1285−99.
- Park T.W., Riethdorf S., Schulz G., Riethdorf L., Wright T., Loning T. Clonal expansion and HPV-induced immortalization are early molecular alterations in cervical carcinogenesis. //Anticancer Res. 2003. Vol.23. P. 155−60.
- Park T.W., Richart R.M., Sun X. W, Wright T.C. Jr. Association between human papillomavirus type and clonal status of cervical squamous intraepithelial lesions. //J Natl Cancer Inst. 1996. Vol.20. P.355−8.
- Peitsaro P., Johansson B., Syrjanen S. Integrated human papillomavirus type 16 is frequently found in cervical cancer precursors as demonstrated by a novel quantitative real-time PCR technique. //J Clin Microbiol. 2002. Vol.40. P.886−91.
- Pereira-Leal J.B., Alistair N., Miguel C. Seabra Prenylation of Rab GTPases: molecular mechanisms and involvement in genetic disease. //FEBS Letters. 2001. Vol.498. P. 197−200.
- Plug-DeMaggio A.W., Sundsvold T., Wurscher M.A., Koop J.I., Klingelhutz A.J., McDougall J.K. Telomere erosion and chromosomal instability in cells expressing the HPV oncogene 16E6. //Oncogene. 2004. Vol.23. P.3561−71.
- Poignee M., Backsch C., Beer K., Jansen L., Wagenbach N., Stanbridge E.J., Kirchmayr R., Schneider A., Durst M. Evidence for a putative senescence gene locus within the chromosomal region 10pl4-pl5. //Cancer Res. 2001. Vol.61. P.7118−21.
- Ponten J., Adami H.O., Friberg L.G., Gustafsson L., Miller A.B., Parkin M., Sparen P., Trichopoulos D. //Int J Cancer. 1995. Vol.63. P.317.
- Pugh C.W., Ratcliffe P.J. The von Hippel-Lindau tumor suppressor, hypoxia-inducible factor-1 (HIF-1) degradation, and cancer pathogenesis. //Semin. Cancer Biol. 2003.Vol.13. P.83−89.
- Rader J.S., Li Y., Huettner P.C., Xu Z., Gerhard D.S. Cervical cancer suppressor gene is within 1 cM on 6p23. //Genes Chromosomes Cancer. 2000. Vol.27. P.373−9.
- Rader J.S., Gerhard D.S., O’Sullivan M.J., Li Y., Li L., Liapis H., Huettner P.C. Cervical intraepithelial neoplasia III shows frequent allelic loss in 3p and 6p. //Genes Chromosomes Cancer. 1998. Vol.22. P.57−65.
- Rha S.H., Dong S.M., Jen J., Nicol T., Sidransky D. Molecular detection of cervical intraepithelial neoplasia and cervical carcinoma by microsatellite analysis of Papanicolaou smears. //Int J Cancer. 2001. Vol.93. P.424−9.
- Rosty C., Couturier J., Vincent-Salomon A., Genin P., Freneaux P., Sigal-Zafrani B., Sastre-Garau X. Overexpression/amplification of HER-2/neu is uncommon in invasive carcinoma of the uterine cervix. //Int J Gynecol Pathol. 2004. Vol.23. P. 13−7.
- Saiki R., Nagata A., Kainou T., Matsuda H., Kawamukai M. Characterization of solanesyl and decaprenyl diphosphate synthases in mice and humans. //FEBS J. 2005. Vol.272. P.5606−22.
- Salaun P., Rannou Y., Prigent C. Cdkl, Plks, Auroras, and Neks: the mitotic bodyguards. //Adv Exp Med Biol. 2008. Vol.617. P.41−56.
- Samoylova E.V., Shaikhaiev G.O., Petrov S.V., Kisseljova N.P., Kisseljov F.L. HPV infection in cervical-cancer cases in Russia. //Int J Cancer. 1995. Vol.61. P.337−41.
- Sandhu A.K., Hubbard K., Kaur G.P., Jha K.K., Ozer H.L., Athwal R.S. Senescence of immortal human fibroblasts by the introduction of normal human chromosome 6. //Proc Natl Acad Sci USA. 1994. Vol.91. P.5498−502.
- Scheffner M., Werness B.A., Huibregtse J.M., Levine A.J., Howley P.M. The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. //Cell. 1990. Vol.63. P. l 129−36.
- Schiffman M., Castle P.E., Jeronimo J., Rodriguez A.C., Wacholder S. Human papillomavirus and cervical cancer. //Lancet. 2007. Vol.370. P.890−907.
- Sinensky M. Functional aspects of polyisoprenoid protein substituents: roles in proteinprotein interaction and trafficking. //Biochimica et Biophysica Acta. 2000. Vol.1529. P.203−209.
- Skomedal H., Forus A., Holm R. Deregulation of D-type cyclins in uterine cancers. Cyclin D1/D3 is differentially expressed in cervical cancer. //Anticancer Res. 2003. Vol.23. P.3929−35.
- Skomedal H., Helland A., Kristensen G.B., Holm R., Borresen-Dale A.L. Allelic imbalance at chromosome region 1 lq23 in cervical carcinomas. //Eur J Cancer. 1999. Vol.35. P.659−63.
- Skyldberg B., Fujioka K., Hellstrom A.C., Sylven L., Moberger B., Auer G. Human papillomavirus infection, centrosome aberration, and genetic stability in cervical lesions. //Mod Pathol. 2001. Vol.14. P.279−84.
- Smith J.S., Lindsay L., Hoots B. et al. Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions: a meta-analysis update. //Int J Cancer. 2007. Vol.121. P.621−32.
- Spriggs A.I., Boddington M.M., Clarke C.M. Carcinoma-in-situ of the cervix uteri. Some cytogenetic observations. Lancet. 1962. Vol.1. P.1383−4.
- Spriggs A.I., Cowdell R.H. Ring chromosomes in carcinoma in situ of the cervix as evidence of clonal growth. //J Obstet Gynaecol Br Commonw. 1972. Vol.79. P.833−40. '
- Srivenugopal K.S., Ali-Osman F. The DNA repair protein, 0(6)-methylguanine-DNA methyltransferase is a proteolytic target for the E6 human papillomavirus oncoprotein.192. //Oncogene. 2002. Vol.21. P.5940−5.
- Stark M., Wichman C., Avivi I., Assaraf Y.G. Aberrant splicing of folylpolyglutamate synthetase as a novel mechanism of antifolate resistance in leukemia. //Blood. 2009. Vol.113. P.4362−9.
- Storchova Z., Pellman D. From polyploidy to aneuploidy, genome instability and cancer. //Nat Rev Mol Cell Biol. 2004. Vol.5. P.45−54.
- Su Т.Н., Wang J.C., Tseng H.H., Chang C.P., Chang T.A., Wei H.J., Chang J.G. Analysis of FHIT transcripts in cervical and endometrial cancers. //Int J Cancer. 1998. Vol.76. P.216−22.
- Suzuki Y., Yamashita R., Shirota M., Sakakibara Y., Chiba J., Mizushima-Sugano J., Nakai K., Sugano S. Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions. //Genome Res. 2004. Vol. l4. P. 1711−8.
- Tan O.L., Whitbread A.K., Clements J.A., Dong Y. Kallikrein-related peptidase (KLK) family mRNA variants and protein isoforms in hormone-related cancers: do they have a function? //Biol Chem. 2006. Vol.387. P.697−705.
- Therman E., Denniston C., Nieminen U., Buchler D.A., Timonen S. X chromatin, endomitoses, and mitotic abnormalities in human cervical cancer. //Cancer Genet Cytogenet. 1985. Vol.16. P. l-11.
- Thiagalingam S., Laken S., Willson J.K., Markowitz S.D., Kinzler K.W., Vogelstein В., Lengauer C. Mechanisms underlying losses of heterozygosity in human colorectal cancers. //Proc Natl Acad Sci USA. 2001. Vol.98. P.2698−702.
- Thomas D.B., Qin Q., Kuypers J. et al. Human papillomavirus and cervical cancer in Bangkok. II. Risk factors for in situ and invasive squamous cell cervical carcinomas. //American Journal of Epidemiology. 2001. Vol.153. P.732−739.
- Tsai T.-C. and Chen S.-L. The biochemical and biological functions of human papillomavirus type 16 E5 protein.//Arch Virol. 2003. Vol.148. P.1445−1453.
- Veldman T., Liu X., Yuan H., Schlegel R. Human papillomavirus E6 and Myc proteins associate in vivo and bind to and cooperatively activate the telomerase reverse transcriptase promoter. //Proc Natl Acad Sci USA. 2003. Vol.100. P.8211−6.
- Venter J.C., Adams M.D., Myers E.W. et al. The sequence of the human genome. Science. 2001. Vol.291. P.1304−51.
- Walboomers J.M., Meijer C.J., Steenbergen R.D., van Duin M., Helmerhorst T.J., Snijders P.J. Human papillomavirus and the development of cervical cancer: concept of carcinogenesis. //Ned Tijdschr Geneeskd. 2000. Vol.144. P. 1671−4.
- Wan T.S., Chan L.C., Ngan H.Y., Tsao S.W. High frequency of telomeric associations in human ovarian surface epithelial cells transformed by human papilloma viral oncogenes. //Cancer Genet Cytogenet. 1997. Vol.95. P. 166−72.
- Weissenbach J., Gyapay G., Dib C., Vignal A., Morissette J., Millasseau P., Vaysseix G., Lathrop M. A second-generation linkage map of the human genome. //Nature. 1992. P.359. P.794−801.
- Werness, B.A., Levine, A.J. & Howley, P.M. Association of human papillomavirus types 16 and 18 E6 proteins with p53. //Science. 1990. Vol.248. P.76−79.
- Wentzensen N., Ridder R., Klaes R., Vinokurova S., Schaefer U., Doeberitz M.K. Characterization of viral-cellular fusion transcripts in a large series of HPV16 and 18 positive anogenital lesions. //Oncogene. 2002. Vol.21. P.419−26.
- Wilting S.M., de Wilde J., Meijer C.J., Berkhof J., Yi Y., van Wieringen W.N., Braakhuis
- B.J., Meijer G.A., Ylstra B., Snijders .PJ., Steenbergen R.D. Integrated genomic and transcriptional profiling identifies chromosomal loci with altered gene expression in cervical cancer. //Genes Chromosomes Cancer. 2008. Vol.47. P.890−905.
- Wilting S.M., Steenbergen R.D., Tijssen M., van Wieringen W.N., Helmerhorst T.J., van Kemenade F.J., Bleeker M.C., van de Wiel M.A., Carvalho B., Meijer G.A., Ylstra B., Meijer
- C.J., Snijders P.J. Chromosomal signatures of a subset of high-grade premalignant cervical lesions closely resemble invasive carcinomas. //Cancer Res. 2009. Vol.69. P.647−55.
- Wong Y.F., Chung T.K., Cheung T.H., Tam P.O., Chang A.M. Frequent loss of heterozygosity of chromosome 3 short arm detected by PCR-based microsatellite polymorphisms in cervical squamous cell carcinoma. //Cancer Lett. 1997. Vol.115. P.161−4.
- Yang Y.C., Spalholz B.A., Rabson M.S., Howley P.M. Dissociation of transforming and trans-activation functions for bovine papillomavirus type 1. //Nature. 1985. Vol.318. P.575−7.
- Yokota J., Tsukada Y., Nakajima T., Gotoh M., Shimosato Y., Mori N., Tsunokawa Y., Sugimura T., Terada M. Loss of heterozygosity on the short arm of chromosome 3 in carcinoma of the uterine cervix. //Cancer Res. 1989. Vol.49. 3598−601.
- Yoshino K., Enomoto T., Nakamura T., Sun H., Ozaki K., Nakashima R., Wada H., Saitoh J., Watanabe Y., Noda K., Murata Y. FHIT alterations in cancerous and non-cancerous cervical epithelium. //Int J Cancer. 2000. Vol.85. P.6−13.
- Zhang Z., Gerhard D.S., Nguyen L., Li J., Traugott A., Huettner P.C., Rader J.S. Fine mapping and evaluation of candidate genes for cervical cancer on llq23. //Genes Chromosomes Cancer. 2005. Vol.43. P.95−103.
- Zhou H., Kuang J., Zhong L., Kuo W.L., Gray J.W., Sahin A., Brinkley B.R., Sen S. Tumour amplified kinase STK15/BTAK induces centrosome amplification, aneuploidy and transformation. //Nat Genet. 1998. Vol.20. P. 189−93.1. Благодарности