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This study molecularly characterizes HGSOC patients from two distinct groups of chemotherapy responders (good vs. poor).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Following primary debulking surgery and intravenous carboplatin\/paclitaxel, women with stage III\u2013IV HGSOC were grouped by response. Patients in the good response (GR) and poor response (PR) groups respectively had a progression\u2010free intervals (PFI) of \u226512 and \u22646\u00a0months. Analysis of surgical specimens interrogated genomic and immunologic features using whole exome sequencing. RNA\u2010sequencing detected gene expression outliers and inference of immune infiltrate, with validation by targeted NanoString arrays. PD\u2010L1 expression was scored by immunohistochemistry (IHC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 39 patient samples were analyzed (GR\u00a0=\u00a020; PR\u00a0=\u00a019). Median PFI for GR and PR patient cohorts was 32 and 3\u00a0months, respectively. GR tumors were enriched for loss\u2010of\u2010function <jats:italic>BRCA2<\/jats:italic> mutations and had a significantly higher nonsynonymous mutation rate compared to PR tumors (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.001). Samples from the PR cohort were characterized by mutations in <jats:italic>MGA<\/jats:italic> and <jats:italic>RAD51B<\/jats:italic> and trended towards a greater rate of amplification of <jats:italic>PIK3CA<\/jats:italic>, <jats:italic>MECOM<\/jats:italic>, and <jats:italic>ATR<\/jats:italic> in comparison to GR tumors. Gene expression analysis by NanoString correlated increased <jats:italic>PARP4<\/jats:italic> with PR and increased <jats:italic>PD<\/jats:italic>\u2010<jats:italic>L1<\/jats:italic> and <jats:italic>EMSY<\/jats:italic> with GR. There was greater tumor immune cell infiltration and higher immune cell PD\u2010L1 protein expression in the GR group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our research demonstrates that tumors from HGSOC patients responding poorly to first line chemotherapy have a distinct molecular profile characterized by actionable drug targets including PARP4.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.3831","type":"journal-article","created":{"date-parts":[[2021,4,3]],"date-time":"2021-04-03T09:43:27Z","timestamp":1617443007000},"page":"3045-3058","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Tumor genomic, transcriptomic, and immune profiling characterizes differential response to first\u2010line platinum chemotherapy in high grade serous ovarian 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