| Autor: |
Anca Nastase, Amit Mandal, Shir Kiong Lu, Hima Anbunathan, Deborah Morris-Rosendahl, Yu Zhi Zhang, Xiao-Ming Sun, Spyridon Gennatas, Robert C. Rintoul, Matthew Edwards, Alex Bowman, Tatyana Chernova, Tim Benepal, Eric Lim, Anthony Newman Taylor, Andrew G. Nicholson, Sanjay Popat, Anne E. Willis, Marion MacFarlane, Mark Lathrop, Anne M. Bowcock, Miriam F. Moffatt, William O. C. M. Cookson |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Scientific Reports, Vol 11, Iss 1, Pp 1-15 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2045-2322 |
| DOI: |
10.1038/s41598-021-98414-w |
| Popis: |
Abstract Pleural mesothelioma is an aggressive malignancy with limited effective therapies. In order to identify therapeutic targets, we integrated SNP genotyping, sequencing and transcriptomics from tumours and low-passage patient-derived cells. Previously unrecognised deletions of SUFU locus (10q24.32), observed in 21% of 118 tumours, resulted in disordered expression of transcripts from Hedgehog pathways and the T-cell synapse including VISTA. Co-deletion of Interferon Type I genes and CDKN2A was present in half of tumours and was a predictor of poor survival. We also found previously unrecognised deletions in RB1 in 26% of cases and show sub-micromolar responses to downstream PLK1, CHEK1 and Aurora Kinase inhibitors in primary mesothelioma cells. Defects in Hippo pathways that included RASSF7 amplification and NF2 or LATS1/2 mutations were present in 50% of tumours and were accompanied by micromolar responses to the YAP1 inhibitor Verteporfin. Our results suggest new therapeutic avenues in mesothelioma and indicate targets and biomarkers for immunotherapy. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
|
Nepřihlášeným uživatelům se plný text nezobrazuje |
K zobrazení výsledku je třeba se přihlásit.
|
