The spectrum of somatic mutations in high-risk acute myeloid leukaemia with -7/del(7q).

-7/del(7q) occurs in half of myeloid malignancies with adverse-risk cytogenetic features and is associated with poor survival. We identified the spectrum of mutations that co-occur with -7/del(7q) in 40 patients with de novo or therapy-related myeloid neoplasms. -7/del(7q) leukaemias have a distinct mutational profile characterized by low frequencies of alterations in genes encoding transcription factors, cohesin and DNA-methylation-related proteins.

Genome-wide association study to identify novel loci associated with therapy-related myeloid leukemia susceptibility.

Therapy-related acute myeloid leukemia (t-AML) is a rare but fatal complication of cytotoxic therapy. Whereas sporadic cancer results from interactions between complex exposures and low-penetrance alleles, t-AML results from an acute exposure to a limited number of potent genotoxins. Consequently, we hypothesized that the effect sizes of variants associated with t-AML would be greater than in sporadic cancer, and, therefore, that these variants could be detected even in a modest-sized cohort.

MDM2 SNP309 and TP53 Arg72Pro interact to alter therapy-related acute myeloid leukemia susceptibility.

The p53 tumor suppressor directs the cellular response to many mechanistically distinct DNA-damaging agents and is selected against during the pathogenesis of therapy-related acute myeloid leukemia (t-AML). We hypothesized that constitutional genetic variation in the p53 pathway would affect t-AML risk. Therefore, we tested associations between patients with t-AML (n = 171) and 2 common functional p53-pathway variants, the MDM2 SNP309 and the TP53 codon 72 polymorphism.