Fig. 6 | Nature Communications

Fig. 6

From: CDK4/6 inhibitors target SMARCA4-determined cyclin D1 deficiency in hypercalcemic small cell carcinoma of the ovary

Fig. 6

SCCOHT patient tumors expressed reduced levels of cyclin D1 mRNA and protein. a, b SCCOHT tumors expressed significantly lower CCND1 mRNA levels compared to ovarian high-grade serous carcinomas (HGSCs). Heatmaps (a) and boxplots (b) showing CCND1 and CDK4 mRNA levels obtained from a NanoString gene expression study in SCCOHT patient tumors (n = 17) relative to HGSCs (n = 6). Two-tailed t test, *p < 0.05. c qRT–PCR analysis of an independent cohort of fresh-frozen patient tumor samples show that SCCOHT (n = 5) expressed significantly low levels of CCND1 mRNA (normalized to GAPDH) compared to HGSCs (n = 7). Two-tailed t test, **p < 0.01; ns not significant. d, e SCCOHT patient tumors express low levels of cyclin D1 and retain the RB-proficient/p16-deficient profile associated with positive responses to palbociclib. Immunohistochemistry (IHC) analysis coupled with unbiased automated quantification52 were performed on formalin-fixed paraffin-embedded HGSC (n = 52) and SCCOHT (n = 32; 4 of which were also analyzed by qRT-PCR in Fig. 6c) patient tumors for the expression of indicated key regulators of G1- to S-phase cell cycle. Representative images of the IHC analysis (d) and quantification results (e) are shown. Bar 50 µm; non-parametric Mann–Whitney test, ***p < 0.001, ****p < 0.0001; Error bars: mean ± standard error of mean (s.e.m.)

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