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Author (up) Patch, A.M.; Christie, E.L.; Etemadmoghadam, D.; Garsed, D.W.; George, J.; Fereday, S.; Nones, K.; Cowin, P.; Alsop, K.; Bailey, P.J.; Kassahn, K.S.; Newell, F.; Quinn, M.C.; Kazakoff, S.; Quek, K.; Wilhelm-Benartzi, C.; Curry, E.; Leong, H.S.; Australian, O.C.S.G.; Hamilton, A.; Mileshkin, L.; Au-Yeung, G.; Kennedy, C.; Hung, J.; Chiew, Y.E.; Harnett, P.; Friedlander, M.; Quinn, M.; Pyman, J.; Cordner, S.; O’Brien, P.; Leditschke, J.; Young, G.; Strachan, K.; Waring, P.; Azar, W.; Mitchell, C.; Traficante, N.; Hendley, J.; Thorne, H.; Shackleton, M.; Miller, D.K.; Arnau, G.M.; Tothill, R.W.; Holloway, T.P.; Semple, T.; Harliwong, I.; Nourse, C.; Nourbakhsh, E.; Manning, S.; Idrisoglu, S.; Bruxner, T.J.; Christ, A.N.; Poudel, B.; Holmes, O.; Anderson, M.; Leonard, C.; Lonie, A.; Hall, N.; Wood, S.; Taylor, D.F.; Xu, Q.; Fink, J.L.; Waddell, N.; Drapkin, R.; Stronach, E.; Gabra, H.; Brown, R.; Jewell, A.; Nagaraj, S.H.; Markham, E.; Wilson, P.J.; Ellul, J.; McNally, O.; Doyle, M.A.; Vedururu, R.; Stewart, C.; Lengyel, E.; Pearson, J.V.; Waddell, N.; deFazio, A.; Grimmond, S.M.; Bowtell, D.D. url  openurl
  Title Whole-genome characterization of chemoresistant ovarian cancer Type Journal Article
  Year 2015 Publication Abbreviated Journal Nature  
  Volume 521 Issue 7553 Pages 489-494  
  Keywords  
  Abstract Patients with high-grade serous ovarian cancer (HGSC) have experienced little improvement in overall survival, and standard treatment has not advanced beyond platinum-based combination chemotherapy, during the past 30 years. To understand the drivers of clinical phenotypes better, here we use whole-genome sequencing of tumour and germline DNA samples from 92 patients with primary refractory, resistant, sensitive and matched acquired resistant disease. We show that gene breakage commonly inactivates the tumour suppressors RB1, NF1, RAD51B and PTEN in HGSC, and contributes to acquired chemotherapy resistance. CCNE1 amplification was common in primary resistant and refractory disease. We observed several molecular events associated with acquired resistance, including multiple independent reversions of germline BRCA1 or BRCA2 mutations in individual patients, loss of BRCA1 promoter methylation, an alteration in molecular subtype, and recurrent promoter fusion associated with overexpression of the drug efflux pump MDR1.  
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  Call Number UofT @ ankit.sinha @ Serial 45069  
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