Fig. 3: Strong transcriptional bias (TRB) is a specific feature of XP-C tumors. | Nature Communications

Fig. 3: Strong transcriptional bias (TRB) is a specific feature of XP-C tumors.

From: XPC deficiency increases risk of hematologic malignancies through mutator phenotype and characteristic mutational signature

Fig. 3

a TRB is observed in the majority of trinucleotide contexts of XP-C leukemia samples (n = 6, SEMs are indicated). b TRB is highly pronounced for specific single nucleotide C:G deletions in XP-C leukemia samples (n = 6, SEMs are indicated). c TRB strength depends on the level of gene expression and is most pronounced in highly expressed genes (SEMs are indicated for leukemia; Poisson, two-sided test used for breast sarcoma (n = 1) and rhabdomyosarcoma (n = 1); Wilcoxon signed-rank, two-sided test for leukemia (n = 6), P: ns—nonsignificant, *<0.5, **<0.01, ***<0.001). d Relative mutational signature contribution for mutations separated by transcribed and untranscribed strands in transcriptionally active (FPKM > 2) and silent genes (FPKM < 0.05) of XP-C leukemia. Boxes depict the interquartile range (25–75% percentile), lines—the median, whiskers—1.5× the IQR below the first quartile and above the third quartile. Predominant in XP-C leukemia Signature “C” is depleted on the transcribed strands with functional TC-NER, but relative contribution of signatures “A” and “E” typical for sporadic leukemia is enriched on the transcribed strand (t test, two-sided, paired between transcribed and untranscribed strands in expressed genes (n = 6), P: ns—nonsignificant, *<0.5, **<0.01, ***<0.001). e TRB is highly significant and pronounced in XP-C samples for all six substitution classes in comparison with sporadic cancers (Poisson two-sided test). f The strong TRB observed in XP-C leukemia (n = 6) is caused by transcriptional-coupled repair (TC-NER) but not transcriptional-associated damage. Strong decrease of mutation rate is observed on the genic untranscibed strand for pyrimidines (transcribed for purines, red; right side of transcription start site, TSS), but not on the transcribed strand for pyrimidines (untranscribed for purines, blue) as compared to neighboring intergenic regions (±50 kbp from transcription start site, SEMs are indicated).

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