TY - JOUR T1 - <em>TP53</em> mutations in high grade serous ovarian cancer and impact on clinical outcomes: a comparison of next generation sequencing and bioinformatics analyses JF - International Journal of Gynecologic Cancer JO - Int J Gynecol Cancer SP - 346 LP - 352 DO - 10.1136/ijgc-2018-000087 VL - 29 IS - 2 AU - Victoria Mandilaras AU - Swati Garg AU - Michael Cabanero AU - Qian Tan AU - Chiara Pastrello AU - Julia Burnier AU - Katherine Karakasis AU - Lisa Wang AU - Neesha C Dhani AU - Marcus O Butler AU - Philippe L Bedard AU - Lillian L Siu AU - Blaise Clarke AU - Patricia Ann Shaw AU - Tracy Stockley AU - Igor Jurisica AU - Amit M Oza AU - Stephanie Lheureux Y1 - 2019/02/01 UR - http://ijgc.bmj.com/content/29/2/346.abstract N2 - Objective Mutations in TP53 are found in the majority of high grade serous ovarian cancers, leading to gain of function or loss of function of its protein product, p53, involved in oncogenesis. There have been conflicting reports as to the impact of the type of these on prognosis. We aim to further elucidate this relationship in our cohort of patients.Methods 229 patients with high grade serous ovarian cancer underwent tumor profiling through an institutional molecular screening program with targeted next generation sequencing. TP53 mutations were classified using methods previously described in the literature. Immunohistochemistry on formalin-fixed paraffin embedded tissue was used to assess for TP53 mutation. Using divisive hierarchal clustering, we generated patient clusters with similar clinicopathologic characteristics to investigate differences in outcomes.Results Six different classification schemes of TP53 mutations were studied. These did not show an association with first platinum-free interval or overall survival. Next generation sequencing reliably predicted mutation in 80% of cases, similar to the proportion detected by immunohistochemistry. Divisive hierarchical clustering generated four main clusters, with cluster 3 having a significantly worse prognosis (p&lt;0.0001; log-rank test). This cluster had a higher concentration of gain of function mutations and these patients were less likely to have undergone optimal debulking surgery.Conclusions Different classifications of TP53 mutations did not show an impact on outcomes in this study. Immunohistochemistry was a good predictor for TP53 mutation. Cluster analysis showed that a subgroup of patients with gain of function mutations (cluster 3) had a worse prognosis. ER -