Study Reveals Role of Sex Chromosomes in Cancer Gene Essentiality

Sex chromosomes can affect gene essentiality in cancer cells, highlighting the influence of X and Y chromosomes in cellular and molecular biology, according to a study appearing this week in Genome Research. Human sex differences are caused by gonadal hormone secretions and genes located on the X and Y chromosomes, but it remains challenging to demonstrate the direct effects of sex chromosomes separate from the gonadal hormones. In the study, investigators from the Hebrew University of Jerusalem set out to examine how sex chromosomes modulate gene expression and the outcome of mutations across the genome using the tendency of cancer cell lines to lose or gain sex chromosomes. They inferred the dosage of sex chromosomes in 355 female and 408 male cancer cell lines, using the results to break out the contributions of the Y and X chromosomes to sex-biased gene expression. Using data from genome-wide CRISPR screens, they further identified genes whose essentiality is different between cells depending on the sex chromosomes. "The results show that both the X and Y chromosomes have a global influence on gene expression and the essentiality of genes," the researchers write. "In addition to the implications of our results for studying the differences between males and females, they are relevant to understanding specific disorders and genetic alterations … [including] syndromes with sex chromosome abnormalities … and the mosaic loss of the Y chromosome frequently observed both in cancer cells and during the normal aging process of male individuals."