Genomic and transcriptomic analyses of breast cancer primaries and matched metastases in AURORA, the Breast International Group (BIG) molecular screening initiative
Articolo
Data di Pubblicazione:
2021
Citazione:
Genomic and transcriptomic analyses of breast cancer primaries and matched metastases in AURORA, the Breast International Group (BIG) molecular screening initiative / P. Aftimos, M. Oliveira, A. Irrthum, D. Fumagalli, C. Sotiriou, E. Nili Gal-Yam, M.E. Robson, J. Ndozeng, A. Di Leo, E.M. Ciruelos, E. de Azambuja, G. Viale, E.D. Scheepers, G. Curigliano, J.M. Bliss, J.S. Reis-Filho, M. Colleoni, M. Balic, F. Cardoso, J. Albanell, C. Duhem, S. Marreaud, D. Romagnoli, B. Rojas, A. Gombos, H. Wildiers, A. Guerrero-Zotano, P. Hall, A. Bonetti, K.F. Larsson, M. Degiorgis, S. Khodaverdi, R. Greil, A. Sverrisdottir, M. Paoli, E. Seyll, S. Loibl, B. Linderholm, G. Zoppoli, N.E. Davidson, O.T. Johannsson, P.L. Bedard, S. Loi, S. Knox, D.A. Cameron, N. Harbeck, M. Lasa Montoya, M. Brandão, A. Vingiani, C. Caballero, F.S. Hilbers, L.R. Yates, M. Benelli, D. Venet, M.J. Piccart. - In: CANCER DISCOVERY. - ISSN 2159-8274. - 11:11(2021 Nov), pp. candisc.1647.2020.2796-candisc.1647.2020.2811. [10.1158/2159-8290.CD-20-1647]
Abstract:
AURORA aims to study the processes of relapse in metastatic breast cancer (MBC) by performing multi-omics profiling on paired primary tumors and early-course metastases. Among 381 patients (primary tumor and metastasis pairs: 252 TGS, 152 RNA-Seq, 67 SNP Arrays), we found a driver role for GATA1 and MEN1 somatic mutations. Metastases were enriched in ESR1, PTEN, CDH1, PIK3CA and RB1 mutations; MDM4, MYC amplifications; ARID1A deletions. An increase in clonality was observed in driver genes like ERBB2 and RB1. Intrinsic subtype switching occurred in 36% of cases. Luminal A/B to HER2-Enriched switching was associated with TP53 and/or PIK3CA mutations. Metastases had lower immune score and increased immune permissive cells. High TMB correlated to shorter time to relapse in HR+/HER2- cancers. ESCAT tier I/II alterations were detected in 51% of patients and matched therapy was used in 7%. Integration of multi-omics analyses in clinical practice could impact treatment strategies in MBC.
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
P. Aftimos, M. Oliveira, A. Irrthum, D. Fumagalli, C. Sotiriou, E. Nili Gal-Yam, M.E. Robson, J. Ndozeng, A. Di Leo, E.M. Ciruelos, E. de Azambuja, G. Viale, E.D. Scheepers, G. Curigliano, J.M. Bliss, J.S. Reis-Filho, M. Colleoni, M. Balic, F. Cardoso, J. Albanell, C. Duhem, S. Marreaud, D. Romagnoli, B. Rojas, A. Gombos, H. Wildiers, A. Guerrero-Zotano, P. Hall, A. Bonetti, K.F. Larsson, M. Degiorgis, S. Khodaverdi, R. Greil, A. Sverrisdottir, M. Paoli, E. Seyll, S. Loibl, B. Linderholm, G. Zoppoli, N.E. Davidson, O.T. Johannsson, P.L. Bedard, S. Loi, S. Knox, D.A. Cameron, N. Harbeck, M. Lasa Montoya, M. Brandão, A. Vingiani, C. Caballero, F.S. Hilbers, L.R. Yates, M. Benelli, D. Venet, M.J. Piccart
Link alla scheda completa: