Publication Date:
2015-12-03
Description:
There is a striking male predominance in hematologic malignancies, as well as many solid tumors, but this sex bias is not understood. US males carry an age-adjusted increased risk of 20.4% for developing any cancer, and ≥2:1 male predominance for some cancer types. This risk leads to 〉150,000 excess new cases of cancer in US men annually. We sequenced DNA from blastic plasmacytoid dendritic cell neoplasm (BPDCN), an aggressive leukemia with significant male predominance (〉3:1 M:F). The splicing factor ZRSR2, located on chrX, had acquired loss-of-function mutations in ~30% of BPDCNs, strikingly all from males (P50% of the excess male risk of BPDCN and 20% of the excess male risk of MDS are associated with ZRSR2 mutation. We termed these genes 'EXITS', for E scape from X -I nactivation T umor S uppressors. A previous study in T-ALL identified KDM6A (UTX) as a possible EXITS gene (Van der Meulen, Blood 2015). To query for EXITS genes in an unbiased manner, we designed computational algorithms to test for male predominance of chrX loss-of-function alterations (SNV, InDel, or copy number loss) in 〉4100 cancers of 21 types from The Cancer Genome Atlas (TCGA). We discovered putative EXITS genes that were mutated more often in males than females (P
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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