Data folder for X-Ra (https://github.com/isglobal-brge/Supplementary-Material/tree/master/Caceres_2024)

X-chromosome inactivation (XCI) is a fundamental mechanism to compensate for gene dosage differences between sexes. Surveying methylation levels over inactivated regions, we establish quantitative levels of defective XCI as a new source of interindividual variation among female tumors, characterized by strong XIST downregulation, and upregulation and enrichment of silenced genes. We show that global defective XCI in silenced genes and disruption of XCI escapees are additive risk factors for cancer in women. Defective XCI maintenance accounts for a 40% attributable risk among 12 different cancers in 3,307 females from the TCGA. Validation data on 523 breast tumors confirm that defective XCI is strongly associated with poor survival and triple-negative subtype. Underlying mechanisms include somatic mutations at TP53, MCY gains, and CSMD1 deletions, suggesting isochromosome 8q formations. Defective XCI is quantifiable in blood and increases with aging and cancer diagnosis. Here we offer the processed data needed for the repository https://github.com/isglobal-brge/Supplementary-Material/tree/master/Caceres_2024 to reproduce our findings.