Understanding the Role of the X Chromosome During Cancer Progression
Half a century ago, Mary Frances Lyon postulated that, to compensate for the difference in chromosomes between females (XX) and males (XY), one X chromosome in female cells during early embryonic stem-cell differentiation is randomly silenced (rendered inactive). The X chromosome inherited from each parent is silenced in 50 per cent of females cells, i.e. 50 per cent of female cells have an active X chromosome of maternal origin and 50 per cent have an active X chromosome of paternal origin. This process is memorized so that it is heritable through subsequent rounds of cell division.
Dr. Alan Spatz, Canada Research Chair in Molecular Pathology, hypothesized that a gene defect would have a different impact on tumour growth depending on whether it affects the active or the inactive X chromosome of a cell. In cutaneous melanoma—the most lethal cancer of the skin—Spatz showed that melanomas in females who died of the disease more frequently have losses on the active X chromosome than melanomas in females who had good clinical outcome. This hypothesis has also been validated in several other types of cancer.
Spatz’s research seeks to gain better insight into the role of the X-chromosome inactivation during the progression of cancers, to study the biological function and regulation of tumour-suppressor genes located on the X chromosome and to identify new X-chromosome-related targets for cancer treatment.
Dr. Alan Spatz’s research on the X-chromosome genetics could open up a new avenue in cancer therapy by identifying new pathways of cancer progression and new therapeutic targets. It is expected that this innovative approach will lead to significant improvements in patient health and treatments that are better adapted to each person.