Fig. 1: Genomic analysis of the XP-C gynecological tumors.

a Family pedigree of the studied patients. Germinal pathogenic variants and diagnoses are indicated. vERMS - vaginal embryonal rhabdomyosarcoma, LAM-2 - acute myeloid leukemia type 2, J-GCT – juvenile granulosa-cell tumor of the ovary, SLCT - Sertoli-Leydig cell tumor. b Tumor mutational burden of single base substitutions (SBS), double base substitutions (DBS) and indels in sporadic Ovarian Granulosa Cell Tumors (n = 45, blue boxplot), XP-C leukemia samples (n = 6, orange boxplot) and XP-C ovarian tumors (n = 3, red boxplot; P-values are indicated, Mann–Whitney U test, two-sided). All the tumors were independent. 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. c Multidimension scaling plots (MDS) for dimensions 1 and 2 and 1 and 3 based on the cosine similarity distances between the SBS trinucleotide-context mutation profiles of individual tumors. XP-C tumors and XP-C iPSCs form a separate group. OGCT—ovarian granulosa cell tumors, iPSCs—induced pluripotent stem cells. d The mean (SE intervals are indicated) transcriptional bias per tumor type (ratio between untranscribed and transcribed strand) for each major type of substitutions (n = 45 for sporadic OGCT, n = 6 for XP-C leukemia, n = 3 for XP-C ovarian independent tumors). e Fraction of mutations for each tumor explained by different COSMIC mutational signatures. f Oncogenic or likely oncogenic mutations in XP-C gynecological tumors according to oncoKB database (m – missense mutation, f – frameshift mutation, s – stop codon gain, n – nonsense mutation, a - promoter activating mutation).