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Your search keyword '"Roxanis, Ioannis"' showing total 3 results
Start Over Author "Roxanis, Ioannis" Journal nature genetics
3 results on '"Roxanis, Ioannis"'

1. SF3B1 hotspot mutations confer sensitivity to PARP inhibition by eliciting a defective replication stress response

Author

Bland, Philip, Saville, Harry, Wai, Patty T., Curnow, Lucinda, Muirhead, Gareth, Nieminuszczy, Jadwiga, Ravindran, Nivedita, John, Marie Beatrix, Hedayat, Somaieh, Barker, Holly E., Wright, James, Yu, Lu, Mavrommati, Ioanna, Read, Abigail, Peck, Barrie, Allen, Mark, Gazinska, Patrycja, Pemberton, Helen N., Gulati, Aditi, Nash, Sarah, Noor, Farzana, Guppy, Naomi, Roxanis, Ioannis, Pratt, Guy, Oldreive, Ceri, Stankovic, Tatjana, Barlow, Samantha, Kalirai, Helen, Coupland, Sarah E., Broderick, Ronan, Alsafadi, Samar, Houy, Alexandre, Stern, Marc-Henri, Pettit, Stephen, Choudhary, Jyoti S., Haider, Syed, Niedzwiedz, Wojciech, Lord, Christopher J., and Natrajan, Rachael

Published
2023
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2. SF3B1hotspot mutations confer sensitivity to PARP inhibition by eliciting a defective replication stress response

Author

Bland, Philip, Saville, Harry, Wai, Patty T., Curnow, Lucinda, Muirhead, Gareth, Nieminuszczy, Jadwiga, Ravindran, Nivedita, John, Marie Beatrix, Hedayat, Somaieh, Barker, Holly E., Wright, James, Yu, Lu, Mavrommati, Ioanna, Read, Abigail, Peck, Barrie, Allen, Mark, Gazinska, Patrycja, Pemberton, Helen N., Gulati, Aditi, Nash, Sarah, Noor, Farzana, Guppy, Naomi, Roxanis, Ioannis, Pratt, Guy, Oldreive, Ceri, Stankovic, Tatjana, Barlow, Samantha, Kalirai, Helen, Coupland, Sarah E., Broderick, Ronan, Alsafadi, Samar, Houy, Alexandre, Stern, Marc-Henri, Pettit, Stephen, Choudhary, Jyoti S., Haider, Syed, Niedzwiedz, Wojciech, Lord, Christopher J., and Natrajan, Rachael

Abstract

SF3B1hotspot mutations are associated with a poor prognosis in several tumor types and lead to global disruption of canonical splicing. Through synthetic lethal drug screens, we identify that SF3B1mutant (SF3B1MUT) cells are selectively sensitive to poly (ADP-ribose) polymerase inhibitors (PARPi), independent of hotspot mutation and tumor site. SF3B1MUTcells display a defective response to PARPi-induced replication stress that occurs via downregulation of the cyclin-dependent kinase 2 interacting protein (CINP), leading to increased replication fork origin firing and loss of phosphorylated CHK1 (pCHK1; S317) induction. This results in subsequent failure to resolve DNA replication intermediates and G2/M cell cycle arrest. These defects are rescued through CINP overexpression, or further targeted by a combination of ataxia-telangiectasia mutated and PARP inhibition. In vivo, PARPi produce profound antitumor effects in multiple SF3B1MUTcancer models and eliminate distant metastases. These data provide the rationale for testing the clinical efficacy of PARPi in a biomarker-driven, homologous recombination proficient, patient population.

Published
2023
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3. Recurrent PTPRB and PLCG1 mutations in angiosarcoma

Author

Behjati, Sam, primary, Tarpey, Patrick S, additional, Sheldon, Helen, additional, Martincorena, Inigo, additional, Van Loo, Peter, additional, Gundem, Gunes, additional, Wedge, David C, additional, Ramakrishna, Manasa, additional, Cooke, Susanna L, additional, Pillay, Nischalan, additional, Vollan, Hans Kristian M, additional, Papaemmanuil, Elli, additional, Koss, Hans, additional, Bunney, Tom D, additional, Hardy, Claire, additional, Joseph, Olivia R, additional, Martin, Sancha, additional, Mudie, Laura, additional, Butler, Adam, additional, Teague, Jon W, additional, Patil, Meena, additional, Steers, Graham, additional, Cao, Yu, additional, Gumbs, Curtis, additional, Ingram, Davis, additional, Lazar, Alexander J, additional, Little, Latasha, additional, Mahadeshwar, Harshad, additional, Protopopov, Alexei, additional, Al Sannaa, Ghadah A, additional, Seth, Sahil, additional, Song, Xingzhi, additional, Tang, Jiabin, additional, Zhang, Jianhua, additional, Ravi, Vinod, additional, Torres, Keila E, additional, Khatri, Bhavisha, additional, Halai, Dina, additional, Roxanis, Ioannis, additional, Baumhoer, Daniel, additional, Tirabosco, Roberto, additional, Amary, M Fernanda, additional, Boshoff, Chris, additional, McDermott, Ultan, additional, Katan, Matilda, additional, Stratton, Michael R, additional, Futreal, P Andrew, additional, Flanagan, Adrienne M, additional, Harris, Adrian, additional, and Campbell, Peter J, additional

Published
2014
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