Both prostate cancer and tRCC share the feature of having a strong driver oncogene on chromosome X. An emerging interest in our laboratory is in using both of these cancers as models to understand how genetic alterations – specifically on the sex chromosomes – may underlie sex differences in cancer incidence or pathogenesis.

Through a pan-cancer genomic analysis, we recently reported that a subset of male cancers can somatically activate the expression of XIST, a normally female-exclusive transcript responsible for dosage compensation of genes on the X chromosome. In ongoing work, we are functionally studying the implications of somatic XIST activation in males and are employing genomic analyses to understand how X-chromosome inactivation can be somatically dysregulated in cancer.