Sex chromosome loss and the pseudoautosomal region genes in hematological malignancies

Abstract

Cytogenetic aberrations, such as chromosomal translocations, aneuploidy, and amplifications, are frequently detected in hematological malignancies. For many of the common autosomal aberrations, the mechanisms underlying their roles in cancer development have been well-characterized. On the contrary, although loss of a sex chromosome is observed in a broad range of hematological malignancies, how it cooperates in disease development is less understood. Nevertheless, it has been postulated that tumor suppressor genes reside on the sex chromosomes. Although the X and Y sex chromosomes are highly divergent, the pseudoautosomal regions are homologous between both chromosomes. Here, we review what is currently known about the pseudoautosomal region genes in the hematological system. Additionally, we discuss implications for haploinsufficiency of critical pseudoautosomal region sex chromosome genes, driven by sex chromosome loss, in promoting hematological malignancies. Because mechanistic studies on disease development rely heavily on murine models, we also discuss the challenges and caveats of existing models, and propose alternatives for examining the involvement of pseudoautosomal region genes and loss of a sex chromosome in vivo. With the widespread detection of loss of a sex chromosome in different hematological malignances, the elucidation of the role of pseudoautosomal region genes in the development and progression of these diseases would be invaluable to the field.

Renal oncocytoma characterized by the defective complex I of the respiratory chain boosts the synthesis of the ROS scavenger glutathione

“…Patient case 2 featured the highest number of losses on chromosomes 1, 14, 19, 21, and a partial loss of chromosome 7. The sex chromosome loss suggests an involvement of pseudo autosomal regions, which have been the prime candidates for harboring tumor suppressors [ 20 ].…”

Chromosome Missegregation and Aneuploidy Induction in Human Peripheral Blood Lymphocytes In vitro by Low Concentrations of Chlorpyrifos, Imidacloprid and α‐Cypermethrin

“…Pioneer studies of chromosome loss in cultured lymphocytes indicated that susceptibility to loss is nonrandom. In respect to that, sex chromosomes are most susceptible, with incidence of X loss of heterozigosity in females and Y loss of heterozigosity in males rising with age (Jacobs et al, ; Jacobs et al, ; Galloway and Buckton, ; Weng et al, ). There is a basic hypothesis that states that a loss of a smaller or heterochromatin‐rich chromosome with less actively transcribed genes is more frequently missegregated since huger parts of heterochromatin between homologs may result in asynchrony in replication, which may contribute to misalignment and malsegregation.…”

When the Lyon(ized chromosome) roars: ongoing expression from an inactive X chromosome

“…Moreover, an over-abundance of 47,XXY males also develop lupus, implicating the presence of the inactive X as a risk factor for this disorder. While a full assessment of the many potential impacts of the X on [6] or with ageing [7] a See text for additional discussion and references. rstb.royalsocietypublishing.org Phil.…”

“…Impact of genes on the inactive X. Xa, active X; Xi, inactive X; X m , maternal X; X p , paternal X; PAR, pseudoautosomal region. [6] or with ageing [7] a See text for additional discussion and references. b Imprinted genes are reported for a small number of genes in somatic tissue of mouse X but have not yet been identified on the human X. rstb.royalsocietypublishing.org Phil.…”