Fig. 2: Genomic characterization, somatic mutational landscape, and DNA methylation profiles of the two retinoblastoma subtypes. | Nature Communications

Fig. 2: Genomic characterization, somatic mutational landscape, and DNA methylation profiles of the two retinoblastoma subtypes.

From: A high-risk retinoblastoma subtype with stemness features, dedifferentiated cone states and neuronal/ganglion cell gene expression

Fig. 2

a Pattern of somatic copy-number alterations in subtype 1 (top, n = 38) and subtype 2 (bottom, n = 58) retinoblastomas. b Boxplots comparing genomic instability between subtype 1 tumors (n = 38) and subtype 2 tumors (n = 58). Among the subtype 2 tumors, non-MYCN-amplified (n = 48) and MYCN-amplified (n = 10) tumors are also shown. Significant differences were tested by two-sided Wilcoxon tests for Subtype 1 vs Subtype 2: p = 3.3 × 10−7; Subtype 1 vs Subtype 2 non-MYCN: p = 1.2 × 10−7; Subtype 1 vs Subtype 2 MYCN-amplified: p = 0.147; and Subtype 2 non-MYCN-amplified vs Subtype 2 MYCN-amplified: p = 0.014. c Boxplots comparing the number of somatic mutations between subtype 1 tumors (n = 25) and subtype 2 tumors (n = 41). Among the subtype 2 tumors, non-MYCN-amplified (n = 33) and MYCN-amplified (n = 8) tumors are also shown. Significance differences were tested by two-sided Wilcoxon tests for Subtype 1 vs Subtype 2: p = 8.1 × 10−7; Subtype 1 vs Subtype 2 non-MYCN-amplified: p = 3.5 × 10−6; Subtype 1 vs Subtype 2 MYCN-amplified: p = 0.001; and Subtype 2 non-MYCN-amplified vs Subtype 2 MYCN-amplified: p = 0.775. b, c In the boxplots, the central mark indicates the median and the bottom and top edges of the box the 25th and 75th percentiles. The whiskers are the smaller of 1.5 times the interquartile range or the length of the 25th percentiles to the smallest data point or the 75th percentiles to the largest data point. Data points outside the whiskers are outliers. Note: p ≥ 0.05 (ns), p < 0.05 (*), p < 0.01 (**), p < 0.001 (***), p < 0.0001 (****). d Somatic mutations of the three genes recurrently altered by tumor subtype. For RB1 are indicated the germline mutations. MYCN amplifications, 1q gains, and 16q losses are also shown. e Heatmap of the 6607 differentially methylated CpGs (difference of methylation level >0.2, adjusted p < 0.05, two-sided Wilcoxon test and BH correction) between subtype 1 and subtype 2. f Distribution, in subtype 2 as compared to subtype 1, of hypomethylated CpGs (upper panel) and hypermethylated CpGs (lower panel), by CpG content and neighborhood context. g Density plots showing the distribution of methylation levels of the differentially methylated CpGs located in CpG islands (upper panel) and outside CpG islands (lower panel).

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