Studies of familial PV have shown that the JAK2 V617F mutation is acquired somatically [39], [40], but have suggested that mutation in another gene may precede the JAK2 mutation in PV.
The finding of Theocharides et al. that 70% of JAK2V617F-positive MPN patients went on to develop JAK2V617F-negative acute myeloid leukemia (AML), suggests that additional predisposing factors may precede the JAK2 mutation.
Our results suggest that DNMT3a mutations may precede the development of AML.
Because aflatoxin-mediated mutations may precede HCC by several years, the effects of reducing aflatoxin exposure on HCC incidence may take time to become apparent (Szymañska et al. 2009).
These data indicate that BRCA LOH and TP53 mutation may coexist in epithelial inclusions prior to the appearance of a pathological lesion in ovaries from BRCA heterozygotes, and that TP53 mutation may precede BRCA LOH in some cases.
From a molecular genetic perspective, these data support the inference drawn from analysis of the prophylactic oophorectomy specimens, that loss of the wild-type BRCA allele may precede or follow TP53 mutation during the early stages of BRCA-associated ovarian tumorigenesis, but that in either case, these genetic events are closely linked.
More recently, WGS has been applied to investigate the evolution of drug resistance based on the hypothesis that additional mutational events may precede or occur concurrently with known resistance conferring mutations [ 4– 8].
Transient neonatal hypoglycemia (15% of mutation carriers) may precede the onset of diabetes at a later age.
Aberrant DNA methylation occurs early in carcinogenesis, suggesting that DNA methylation alterations may precede classical transforming events such as gene mutations.
CSF1R's role as a microglial regulator and the functional deficits associated with CSF1R mutations supports the hypothesis that microglia dysfunction may precede the accumulation of axonal spheroids in HDLS.
