Imaging-genomic pipeline for identifying gene mutations using three-dimensional intra-tumor heterogeneity features

This paper presents an imaging-genomic pipeline to derive three-dimensional intra-tumor heterogeneity features from contrast-enhanced CT images and correlates them with gene mutation status. The pipeline has been demonstrated using CT scans of patients with clear cell renal cell carcinoma (ccRCC) from The Cancer Genome Atlas. About 15% of ccRCC cases reported have BRCA1-associated protein 1 (BAP1) gene alterations that are associated with high tumor grade and poor prognosis. We hypothesized that BAP1 mutation status can be detected using computationally derived image features. The molecular data pertaining to gene mutation status were obtained from the cBioPortal. Correlation of the image features with gene mutation status was assessed using the Mann-Whitney-Wilcoxon rank-sum test. We also used the random forests classifier in the Waikato Environment for Knowledge Analysis software to assess the predictive ability of the computationally derived image features to discriminate cases with BAP1 mutations for ccRCC. Receiver operating characteristics were obtained using a leave-one-out-cross-validation procedure. Our results show that our model can predict BAP1 mutation status with a high degree of sensitivity and specificity. This framework demonstrates a methodology for noninvasive disease biomarker detection from contrast-enhanced CT images.