DNA copy number profiling reveals extensive genomic loss in hereditary BRCA1 and BRCA2 ovarian carcinomas
Por:
Kamieniak, MM, Munoz-Repeto, I, Rico, D, Osorio, A, Urioste, M, Garcia-Donas, J, Hernando, S, Robles-Diaz, L, Cajal, TRY, Cazorla, A, Saez, R, Garcia-Bueno, JM, Domingo, S, Borrego, S, Palacios, J, van de Wiel, MA, Ylstra, B, Benitez, J, Garcia, MJ
Publicada:
30 abr 2013
Resumen:
Background: Few studies have attempted to characterise genomic changes occurring in hereditary epithelial ovarian carcinomas (EOCs) and inconsistent results have been obtained. Given the relevance of DNA copy number alterations in ovarian oncogenesis and growing clinical implications of the BRCA-gene status, we aimed to characterise the genomic profiles of hereditary and sporadic ovarian tumours.
Methods: High-resolution array Comparative Genomic Hybridisation profiling of 53 familial (21 BRCA1, 6 BRCA2 and 26 non-BRCA1/2) and 15 sporadic tumours in combination with supervised and unsupervised analysis was used to define common and/or specific copy number features.
Results: Unsupervised hierarchical clustering did not stratify tumours according to their familial or sporadic condition or to their BRCA1/2 mutation status. Common recurrent changes, spanning genes potentially fundamental for ovarian carcinogenesis, regardless of BRCA mutations, and several candidate subtype-specific events were defined. Despite similarities, greater contribution of losses was revealed to be a hallmark of BRCA1 and BRCA2 tumours.
Conclusion: Somatic alterations occurring in the development of familial EOCs do not differ substantially from the ones occurring in sporadic carcinomas. However, some specific features like extensive genomic loss observed in BRCA1/2 tumours may be of clinical relevance helping to identify BRCA-related patients likely to respond to PARP inhibitors.
Filiaciones:
Kamieniak, MM:
Spanish Natl Canc Res Ctr CNIO, Madrid 28029, Spain
Munoz-Repeto, I:
Spanish Natl Canc Res Ctr CNIO, Madrid 28029, Spain
Rico, D:
Spanish Natl Canc Res Ctr CNIO, Struct Computat Biol Grp, Madrid 28029, Spain
Osorio, A:
Spanish Natl Canc Res Ctr CNIO, Madrid 28029, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid 28029, Spain
Urioste, M:
Spanish Natl Canc Res Ctr CNIO, Madrid 28029, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid 28029, Spain
Garcia-Donas, J:
Spanish Natl Canc Res Ctr CNIO, Prostate Canc & Genitourinary Tumors Clin Res Uni, Madrid 28029, Spain
Ctr Integral Oncol Clara Campal, Madrid 28050, Spain
Hernando, S:
Fdn Hosp Alcorcon, Dept Oncol, Alcorcon 28922, Spain
Robles-Diaz, L:
Hosp Univ 12 Octubre, Familial Canc Unit, Madrid 28041, Spain
Hosp Univ 12 Octubre, Dept Med Oncol, Madrid 28041, Spain
Cajal, TRY:
Hosp Santa Creu & Sant Pau, Dept Med Oncol, Barcelona 08025, Spain
Cazorla, A:
Fdn Jimenez Diaz, Dept Pathol, E-28040 Madrid, Spain
Saez, R:
Hosp Donostia, Dept Genet, San Sebastian, Spain
Garcia-Bueno, JM:
Hosp Gen Albacete, Dept Oncol, Albacete 02008, Spain
Domingo, S:
Spanish Natl Canc Res Ctr CNIO, Madrid 28029, Spain
Borrego, S:
Hosp Virgen Rocio, Dept Genet, Seville 41013, Spain
Palacios, J:
Hosp Univ Ramon & Cajal, Dept Pathol, Madrid 28049, Spain
van de Wiel, MA:
Vrije Univ Amsterdam, Med Ctr, Dept Epidemiol & Biostat, NL-1081 HZ Amsterdam, Netherlands
Ylstra, B:
Vrije Univ Amsterdam, Med Ctr, Dept Pathol, NL-1081 HZ Amsterdam, Netherlands
Benitez, J:
Spanish Natl Canc Res Ctr CNIO, Madrid 28029, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid 28029, Spain
Garcia, MJ:
Spanish Natl Canc Res Ctr CNIO, Madrid 28029, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid 28029, Spain
Green Published, Hybrid Gold
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