Cirilo, PDRREFERÊNCIAS223Narayan G, Scotto L, Neelakantan V et al. Protocadherin PCDH10, involved in tumor progression, isa frequent and early target of promoter hypermethylation in cervical cancer. GenesChromosomes Cancer, 48, 983-992, 2009.Nezhad MH, Drieschner N, Helms S et al. 6p21 rearrangements in uterine leiomyomas targetingHMGA1. Cancer Genet Cytogenet, 203, 247-252, 2010.Nikitenko LL, Cross T, Campo L et al. Expression of terminally glycosylated calcitonin receptor-likereceptor in uterine leiomyoma: endothelial phenotype and association with microvascular<strong>de</strong>nsity. Clin Cancer Res, 12, 5648-5658, 2006.Nilbert M, Heim S, Mandahl N et al. Ring formation and structural rearrangements of chromosome 1as secondary changes in uterine leiomyomas with t(12;14)(q14–15;q23–24). Cancer GenetCytogenet, 36, 183–190, 1988.Nilbert M and Heim S. Uterine Leiomyoma Cytogenetics. Genes Chrom Cancer, 2, 3–13, 1990.Nilbert M, Heim S, Mandahl N et al. Characteristic chromosome abnormalities, includingrearrangements of 6p, <strong>de</strong>l(7q), +12, and t(12;14), in 44 uterine leiomyomas. Hum Genet, 85,605-611, 1990.Nishiyama N, Arai E, Nagashio R et al. Copy number alterations in urothelial carcinomas: theirclinicopathological significance and correlation with DNA methylation alterations.Carcinogenesis, 32, 462-469, 2011.Noe M, Kunz G, Herbertz M et al. The cyclic pattern of the immunocytochemical expression ofoestrogen and progesterone receptors in human myometrial and endometrial layers:characterization of the endometrial–subendometrial unit. Human Reproduction, 14, 190–197, 1999.Nowak RA. I<strong>de</strong>ntification of new therapies for leiomyomas: What in vitro studies can tell us. ClinObstet Gynecol, 44, 327-334, 2001.Noyes RW, Hertig AT, Rock J. Dating the endometrial biopsy. Fertil Steril, 1, 3-25, 1950.Numa F, Hirabayashi K, Kawasaki K et al. Syn<strong>de</strong>can-1 expression in cancer of the uterine cervix:association with lymph no<strong>de</strong> metastasis. Int J Oncol, 20, 39-43, 2002.Olshen AB, Venkatraman ES, Lucito R et al. Circular binary segmentation for the analysis of arraybasedDNA copy number data. Biostatistics, 5, 557–572, 2004.O'Neill CJ, McBri<strong>de</strong> HA, Connolly LE et al. Uterine leiomyosarcomas are characterized by high p16,p53 and MIB1 expression in comparison with usual leiomyomas, leiomyoma variants andsmooth muscle tumours of uncertain malignant potential. Histopathol, 50, 851-858, 2007.Oster B, Thorsen K, Lamy P et al. I<strong>de</strong>ntification and validation of highly frequent CpG islandhypermethylation in colorectal a<strong>de</strong>nomas and carcinomas. Int J Cancer, Epub ahead of print,2011.Ozisik YY, Meloni AM, Surti U et al. Inversion (X)(p22q13) in a uterine leiomyoma. Cancer GenetCytogenet, 61, 131-133, 1992.
Cirilo, PDRREFERÊNCIAS224Ozisik YY, Meloni AM, Surti U et al. Involvement of 10q22 in leiomyoma. Cancer Genet Cytogenet,69, 132–135, 1993a.Ozisik YY, Meloni AM, Surti U et al. Deletion of 7q22 in uterine leiomyomas. A cytogenetic review.Cancer Genet Cytogenet, 71, 1-6, 1993b.Ozisik YY, Meloni AM, Stone JF et al. Spontaneous expression of the chromosome fragile site at10q23 in leiomyoma. Cancer Genet Cytogenet, 74, 73-75, 1994.Packenham JP, Du Manoir S, Schrock E et al. Analysis of genetic alterations in uterine leiomyomasand leiomyosarcomas by comparative genomic hybridization. Mol Carcinog, 19, 273-279,1997.Paiva CE, Drigo SA, Rosa FE et al. Absence of transforming growth factor-beta type II receptor isassociated with poorer prognosis in HER2-negative breast tumours. Ann Oncol, 21, 734-740,2010.Pakiz M, Potocnik U, But I. Solitary and multiple uterine leiomyomas among Caucasian women: twodifferent disor<strong>de</strong>rs? Fertil Steril, 94, 2291-2295.Pan CC and Epstein JI. Detection of chromosome copy number alterations in metanephric a<strong>de</strong>nomasby array comparative genomic hybridization. Mod Pathol, 23, 1634-1640, 2010.Pan Q, Luo X, Chegini N. microRNA 21 (miR-21): Response to hormonal therapies and regulatoryfunction in Leiomyoma, transformed Leiomyoma and Leiomyosarcoma cells. Mol HumReprod, 1-35, 2009.Pandis N, Heim S, Bardi G et al. Parallel karyotypic evolution and tumor progression in uterineleiomyoma. Genes Chrom Cancer, 2, 311-317, 1990.Park J, Chen L, Ratnashinge L et al: Deletion polymorphism of UDP-glucuronosyltransferase 2B17and risk of prostate cancer in African American and Caucasian men. Cancer Epi<strong>de</strong>miolBiomarkers Prev, 15, 1473–1478, 2006.Parker WH. Etiology, symptomatology, and diagnosis of uterine myomas. Fertil Steril, 87, 725–36,2007.Parker WH, Fu YS, Berek JS: Uterine sarcoma in patients operated on for presumed leiomyoma andrapidly growing leiomyoma. Obstet Gynecol, 83, 414-418, 1994.Peddada SD, Laughlin SK, Minera K et al. Growth of uterine leiomyomata among premenopausalblack and white women. PNAS, 16, 105, 19887–19892, 2008.Pei-Chieng C, Takahashi A, Hosono N et al. A genome-wi<strong>de</strong> association study i<strong>de</strong>ntifies three lociassociated with susceptibility to uterine fibroids. Nat Genetics, 43, 447-451, 2011.Peng Y, Laser J, Shi G et al. Antiproliferative effects by Let-7 repression of high-mobility group A2 inUterine Leiomyoma. Mol Cancer Res, 6, 663-673, 2008.
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Universidade Estadual Paulista “J
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AGRADECIMENTOSÀ minha orientadora
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LISTA DE FIGURASFigura 1 A - Freqü
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sonda A_14_P131252 que mapeia o gen
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esultante da análise do SAM (Tushe
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Figura 33 Agrupamento hierárquico
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LISTA DE TABELASQuadro 1Relação d
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LISTA DE SIGLAS E ABREVIATURASANG A
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SUMÁRIO1 Introdução ............
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Cirilo, PDRINTRODUÇÃO11. Introdu
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Cirilo, PDRINTRODUÇÃO3dados em li
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Cirilo, PDRINTRODUÇÃO5infertilida
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Cirilo, PDRINTRODUÇÃO7foram despe
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Cirilo, PDRINTRODUÇÃO9(10q24.33),
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Cirilo, PDRINTRODUÇÃO11somente fo
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Cirilo, PDRINTRODUÇÃO13Segundo a
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Cirilo, PDRINTRODUÇÃO15(Sargent e
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Cirilo, PDRINTRODUÇÃO171 geralmen
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Cirilo, PDRINTRODUÇÃO19transcrita
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Cirilo, PDRINTRODUÇÃO21amostras.
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Cirilo, PDRINTRODUÇÃO23evento que
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Cirilo, PDRINTRODUÇÃO25também os
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Cirilo, PDRINTRODUÇÃO27tratamento
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Cirilo, PDRINTRODUÇÃO29Hodge et a
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Cirilo, PDRMATERIAL E MÉTODOS313.
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Cirilo, PDRMATERIAL E MÉTODOS33Tam
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Cirilo, PDRMATERIAL E MÉTODOS35for
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Cirilo, PDRMATERIAL E MÉTODOS370,1
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Cirilo, PDRMATERIAL E MÉTODOS39alt
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Cirilo, PDRMATERIAL E MÉTODOS413)
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Cirilo, PDRRESULTADOS43Tabela 1. Da
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Cirilo, PDRRESULTADOS45ABFigura 1.
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Cirilo, PDRRESULTADOS47Este estudo
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Cirilo, PDRRESULTADOS494.2.1 Caract
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Cirilo, PDRRESULTADOS51Entre as 45
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Cirilo, PDRRESULTADOS53(10%)Cromoss
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Cirilo, PDRRESULTADOS55Cromossomo 1
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Cirilo, PDRRESULTADOS574.2.2 Tumore
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Cirilo, PDRRESULTADOS59Tabela 4. De
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Cirilo, PDRRESULTADOS61629T 629T_A,
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Cirilo, PDRRESULTADOS63279,263-1,48
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Cirilo, PDRRESULTADOS65ABFigura 7.
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Cirilo, PDRRESULTADOS67ABFigura 8 -
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ABCirilo, PDRRESULTADOS69Figura 10.
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Cirilo, PDRRESULTADOS71Figura 11. A
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Cirilo, PDRRESULTADOS73Grupo 1tumor
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Cirilo, PDRRESULTADOS75Figura 14. A
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Cirilo, PDRRESULTADOS77631T_C 99,55
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Cirilo, PDRRESULTADOS794.3 Análise
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Cirilo, PDRRESULTADOS81Tabela 7. Re
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ABCirilo, PDRRESULTADOS83Figura 16.
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Cirilo, PDRRESULTADOS85Figura 17. V
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Cirilo, PDRRESULTADOS87Figura 19. R
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Cirilo, PDRRESULTADOS894.3.1 Análi
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Cirilo, PDRRESULTADOS91Figura 22. A
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Cirilo, PDRRESULTADOS93Entre os cas
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Cirilo, PDRRESULTADOS95Figura 23. A
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Cirilo, PDRRESULTADOS97Tabela 8. Ge
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Cirilo, PDRRESULTADOS99HAPLN1 HAPLN
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Cirilo, PDRRESULTADOS101beta 4MYO10
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Cirilo, PDRRESULTADOS103DIO1 DIO1 d
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Cirilo, PDRRESULTADOS105inhibits CD
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Cirilo, PDRRESULTADOS107CENPK CENPK
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Cirilo, PDRRESULTADOS109pareamento
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Cirilo, PDRRESULTADOS111JUB, ↓MAG
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Cirilo, PDRRESULTADOS113Figura 25.
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Cirilo, PDRRESULTADOS115Figura 27.
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Cirilo, PDRRESULTADOS117Figura 29.
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Cirilo, PDRRESULTADOS1194.5.1 CGH a
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Cirilo, PDRRESULTADOS121Figura 32.
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Cirilo, PDRRESULTADOS123Tabela 10.
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Cirilo, PDRRESULTADOS125
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Cirilo, PDRRESULTADOS1274.5.3.1 Pre
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Cirilo, PDRRESULTADOS129PKP3 - -PRE
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Cirilo, PDRRESULTADOS131Tabela 12.
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Cirilo, PDRRESULTADOS133Perda (1) N
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ABCirilo, PDRRESULTADOS135Figura 33
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Cirilo, PDRRESULTADOS1374.5.3.4 Fre
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Cirilo, PDRRESULTADOS139Tabela 13.
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Cirilo, PDRRESULTADOS1414.5.3.6 An
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Cirilo, PDRRESULTADOS143Tabela 15.
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Cirilo, PDRRESULTADOS145ativação
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ACirilo, PDRRESULTADOS147BFigura 36
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Cirilo, PDRRESULTADOS149Figura 38.
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Cirilo, PDRDISCUSSÃO1515. Discuss
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Cirilo, PDRDISCUSSÃO154informaçõ
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Cirilo, PDRDISCUSSÃO156descritos g
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Cirilo, PDRDISCUSSÃO158uma proteí
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Cirilo, PDRDISCUSSÃO160celulares e
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Cirilo, PDRDISCUSSÃO162apresentado
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Cirilo, PDRDISCUSSÃO164q14). Porta
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Cirilo, PDRDISCUSSÃO166Desde 1991,
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Cirilo, PDRDISCUSSÃO168núcleo das
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Cirilo, PDRDISCUSSÃO170sobre LHFPL
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- Page 231 and 232: Cirilo, PDRREFERÊNCIAS2087. Refer
- Page 233 and 234: Cirilo, PDRREFERÊNCIAS210Brazelle
- Page 235 and 236: Cirilo, PDRREFERÊNCIAS212Churikov
- Page 237 and 238: Cirilo, PDRREFERÊNCIAS214Gannon BR
- Page 239 and 240: Cirilo, PDRREFERÊNCIAS216Holthause
- Page 241 and 242: Cirilo, PDRREFERÊNCIAS218Kazmiercz
- Page 243 and 244: Cirilo, PDRREFERÊNCIAS220Lloret M,
- Page 245: Cirilo, PDRREFERÊNCIAS222Mitra R,
- Page 249 and 250: Cirilo, PDRREFERÊNCIAS226Redon R,
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- Page 253 and 254: Cirilo, PDRREFERÊNCIAS230Ueki K, R
- Page 255 and 256: Cirilo, PDRREFERÊNCIAS232and poly(
- Page 257 and 258: Skubitz KM e Skubitz APJ Lab Clin M
- Page 259 and 260: Dimitrova IK et al. Fertil Steril,9
- Page 261 and 262: 317T_B317T_C13 614T 44 LU prolifera
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- Page 267 and 268: MRPS31, SLC25A15, SUGT1L1 320d-1630
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- Page 275 and 276: ABSTRACTBackground: Uterine leiomyo
- Page 277 and 278: Thus, these findings prompt us to i
- Page 279 and 280: Technologies, Santa Clara, CA). Sta
- Page 281 and 282: mapped at 1p36.13, 1q41, 2q32.1, 2q
- Page 283 and 284: genetic disorder showed the higher
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- Page 287 and 288: egulation of cell cycle. Chegini an
- Page 289 and 290: REFERENCES[1] Baird DD, Dunson DB (
- Page 291 and 292: [37] Luo X, Ding L, Xu J et al. (20
- Page 293 and 294: AArray CGHExpression arrayBtumoral
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Tabel 2. Genes identified on module
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Table S1. Clinical parameters and h
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32 954T 45 M secretory W 12 33,7 18
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16 28184420-30915100 2730680 p11.2
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MYPN hsa-miR-214 -NFKBIL2 - -PKP3 -
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Table S5. Ingenuity Pathways Analys