This mutation was earlier shown to disable the major FG repeat binding site in NTF2 and to abolish the capacity of NTF2 to stimulate nuclear influx of RanGDP through untreated NPCs (Bayliss et al, 1999).
We provide evidence that IGH-BCL2 translocations and CREBBP mutations are early events, whereas MLL2 and TNFRSF14 mutations probably represent late events during disease evolution.
Mutations are early events in carcinogenesis and impaired DNA repair might be a risk factor for many cancers [ 4].
KIT and PDGFRA mutations are early molecular events in GIST development, but those that accumulate during the disease progression are poorly elucidated.
Furthermore, Klampfl et al. showed that in two PMF patients with multiple mutations, the CALR mutations were early events, that is, they had already been present in the proliferative phase of PMF.
It was neither correlated to tumour stage since mutations were detected in plasma of patients with non metastatic tumours, which supports the hypothesis that KRAS2 mutations are early events in pancreatic carcinogenesis (Jimenez et al, 1999).
We have also documented previously that efficient predictors for BRCA1 and BRCA2 mutations are early age of breast cancer onset and number of ovarian cancer cases in the family [ 27].
Clearly, optimal methods need to be applied with the perspective of gaining further knowledge of tumour biology, heterogeneity and to clarify whether mutations are early events at low concentrations or de novo mutations actually do appear along with the development of resistance to a certain therapy.
PIK3CA mutations have been found at similar frequencies in breast ductal carcinoma in situ (DCIS) lesions, DCIS adjacent to invasive ductal carcinoma (IDC), and IDC [ 8], suggesting that these mutations are early events in breast tumorigenesis and therefore may promote transformation of normal breast epithelial cells.
By classifying whether mutations were early clonal (ploidy > 1), late clonal (ploidy = 1) or subclonal (ploidy < 1) in regions of copy number gains, we could assess the relative contributions of these five processes at different times during a cancer's evolution.
