| Texto completo | |
| Autor(es): Mostrar menos - |
Gusev, Alexander
[1, 2]
;
Lawrenson, Kate
[3, 4, 5]
;
Lin, Xianzhi
[3]
;
Lyra, Jr., Paulo C.
[6]
;
Kar, Siddhartha
[7]
;
Vavra, Kevin C.
[3]
;
Segato, Felipe
[8]
;
Fonseca, Marcos A. S.
[3]
;
Lee, Janet M.
[4]
;
Pejovic, Tanya
[9, 10]
;
Liu, Gang
[3]
;
Karlan, Beth Y.
[3]
;
Freedman, Matthew L.
[1]
;
Noushmehr, Houtan
[8, 11]
;
Monteiro, Alvaro N.
[6]
;
Pharoah, Paul D. P.
[7]
;
Pasaniuc, Bogdan
[12, 13, 5]
;
Gayther, Simon A.
[4]
;
Consortium, Ovarian Can Assoc
Número total de Autores: 19
|
| Afiliação do(s) autor(es): Mostrar menos - | [1] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 - USA
[2] Brigham & Womens Hosp, Div Genet, 75 Francis St, Boston, MA 02115 - USA
[3] Cedars Sinai Med Ctr, Womens Canc Program, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 - USA
[4] Cedars Sinai Med Ctr, Dept Biomed Sci, Samuel Oschin Comprehens Canc Inst, Ctr Bioinformat & Funct Genom, Los Angeles, CA 90048 - USA
[5] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biomath, Los Angeles, CA 90095 - USA
[6] H Lee Moffitt Canc Ctr & Res Inst, Canc Epidemiol Program, Tampa, FL - USA
[7] Univ Cambridge, CR UK Dept Oncol, Strangeways Res Lab, Cambridge - England
[8] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, Sao Paulo - Brazil
[9] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 - USA
[10] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97201 - USA
[11] Henry Ford Hosp, Dept Neurosurg, Detroit, MI 48202 - USA
[12] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 - USA
[13] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 - USA
Número total de Afiliações: 13
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Nature Genetics; v. 51, n. 5, p. 815+, MAY 2019. |
| Citações Web of Science: | 2 |
| Resumo | |
We sought to identify susceptibility genes for high-grade serous ovarian cancer (HGSOC) by performing a transcriptome-wide association study of gene expression and splice junction usage in HGSOC-relevant tissue types (N = 2,169) and the largest genome-wide association study available for HGSOC (N =13,037 cases and 40,941 controls). We identified 25 transcriptome-wide association study significant genes, 7 at the junction level only, including LRRC46 at 19q21.32, (P=1 x 10(-9)), CHMP4C at 8q21 (P= 2 x 10(-11)) and a PRC1 junction at 15q26 (P=7 x 10(-9)). In vitro assays for CHMP4C showed that the associated variant induces allele-specific exon inclusion (P= 0.0024). Functional screens in HGSOC cell lines found evidence of essentiality for three of the new genes we identified: HAUS6, KANSL1 and PRC1, with the latter comparable to MYC. Our study implicates at least one target gene for 6 out of 13 distinct genome-wide association study regions, identifying 23 new candidate susceptibility genes for HGSOC. (AU) | |
| Processo FAPESP: | 17/08211-1 - Estudo da origem celular do câncer de ovário usando dados genômicos e epigenômicos em larga escala. |
| Beneficiário: | Marcos Abraão de Souza Fonseca |
| Modalidade de apoio: | Bolsas no Brasil - Programa Capacitação - Treinamento Técnico |
| Processo FAPESP: | 15/07925-5 - Softwares de código aberto contendo ferramentas estatísticas para análise e integração de conjuntos de dados epigenômicos produzidos em alta escala, a fim de decifrar e entender redes reguladoras de câncer |
| Beneficiário: | Houtan Noushmehr |
| Modalidade de apoio: | Auxílio à Pesquisa - Jovens Pesquisadores |