Fig. 5: Hypothesis for relationship between BAP1 dosage, tumor immune microenvironment, and discriminant score.
From: Early genetic evolution of driver mutations in uveal melanoma
BAP1 dosage decreases as BAP1-deficient tumor cells outcompete BAP1-wildtype tumor cells, leading to altered composition of infiltrating immune cells in the tumor immune microenvironment (TIM). Since the 15-GEP includes genes expressed in tumor cells, immune cells or both, inversion of the SVM discriminant score from the Class 1 side to the Class 2 side of decision boundary occurs progressively as the transcriptional effects of BAP1 loss accrue in both tumor and immune cells. This would explain why there is not a strict association between the fraction of cancer cells harboring mutant BAP1 (CCFBAP1) and the discriminant score, as the rate at which the TIM changes following BAP1 loss may differ between individuals. This would also explain why transitional tumors with low discriminant score tend to be small, whereas larger tumors, which have had longer for these transcriptional changes to occur, tend to have high discriminant scores.
