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Additional file 1: Fig. S1. Validation of novel somatic mutations from targeted NGS sequencing by Sanger Sequencing. A Somatic UBR5 mutation detected in sample LGS106. B Somatic TP53 mutation detected in sample LGS105. C Somatic ATRX and EPHA3 mutations were detected in sample LGS119. Fig. S2. Validation of DNM3 somatic nonsynonymous mutations in two LGSOCs by Sanger Sequencing. Fig. S3. Twenty differentially expressed proteins shared between two different cohorts (LGSOC_MDACC_DISOVERY and LGSOC_INOVA_VALIDATION). LGSOC_MDACC: n = 7 long (median = 146 months), n = 7 short (median = 24 months; 531 protein alterations, LIMMA p < 0.05). LGSOC_INOVA: n = 4 long (median = 102 months), n = 2 short (median = 33 months), 294 protein alterations, LIMMA p < 0.05). 20 co-altered, Spearman rho = 0.48 for protein abundance; all alterations trends are concordant except for 3 proteins. Fig. S4. Protein expression associated with patients’ survival. Up-regulation of GTF2F1 and TRIM27 transcripts correlate with better survival. Up-regulation of HBA1 correlates with poor survival. Figures were generated at KMplot website ( https://kmplot.com/analysis/index.php?p=service&cancer=ovar ). Fig. S5. Differentially expressed phosphosites between long-term and short-term survivors. A Heatmap of differentially expressed phosphoproteins between long-term and short-term survivors; LIMMA p < 0.01, fold-change ± 1.5. B Long-term and short-term survivors were separated by principal component analysis (PCA) with differentially expressed phosphoproteins PCA of protein alterations shown in A served to explain 59.1% and 10.4% of the variance between short and long-term survivors. Fig. S6. Correlation of 62 significantly differentially expressed genes with co-quantified proteins.

ObjectiveTo examine clinicopathologic variables associated with survival among women with low-grade (grade 1) serous ovarian carcinoma enrolled in a phase III study.MethodsThis was an ancillary data analysis of Gynecologic Oncology Group protocol 182, a phase III study of women with stage III-IV epithelial ovarian carcinoma treated with carboplatin and paclitaxel compared with triplet or sequential doublet regimens. Women with grade 1 serous carcinoma (a surrogate for low-grade serous disease) were included in the analysis.ResultsAmong the 3,686 enrolled participants, 189 had grade 1 disease. The median age was 56.5 years and 87.3% had stage III disease. The median follow-up time was 47.1 months. Stratification according to residual disease after primary surgery was microscopic residual in 24.9%, 0.1-1.0 cm of residual in 51.3%, and more than 1.0 cm of residual in 23.8%. On multivariate analysis, only residual disease status (P=.006) was significantly associated with survival. Patients with microscopic residual had a significantly longer median progression-free (33.2 months) and overall survival (96.9 months) compared with those with residual 0.1-1.0 cm (14.7 months and 44.5 months, respectively) and more than 1.0 cm of residual disease (14.1 months and 42.0 months, respectively; progression-free and overall survival, P

The oncogene RAS is known to induce genomic instability, leading to cancer development; the underlying mechanism, however, remains poorly understood. To better understand how RAS functions, we measured the activity of the functionally related genes Aurora-A and BRCA2 in ovarian cancer cell lines and tumor samples containing RAS mutations. We found that Aurora-A and BRCA2 inversely controlled RAS-associated genomic instability and ovarian tumorigenesis through regulation of cytokinesis and polyploidization. Over-expression of mutated RAS ablated BRCA2 expresson but induced Aurora-A accumulation at the midbody, leading to abnormal cytokinesis and ultimately chromosomal instability via polyploidy in cancer cells. RAS regulates the expression of Aurora-A and BRCA2 through dysregulated protein expression of farnesyl protein transferase β (FTβ and insulin-like growth factor binding protein 3 (IGFBP-3). Our results suggest that the imbalance in expression of Aurora-A and BRCA2 regulates RAS-induced genomic instability and tumorigensis.