Since BRCA1 has been found to be methylated in WBC genomic DNA, we hypothesized that other breast cancer related genes may also be epigenetically affected.
Then, we carried out an Ingenuity Pathway Analysis (IPA; Figure 6A) to identify pathways that are epigenetically affected in T2D islets according to our methylation profiling data.
A group of genes have been identified as epigenetically affected in NB cell lines; the PIK3CD gene stands out as the most intriguing, since it also carries mutations in primary tumours, two patients with nonsynonymous mutations were identified.
As such, our findings are indicators of large genome-wide changes in transcriptional activities associated with overweight and diabetes, which may be involved in an epigenetically affected propensity for these common disorders.
HSP90 can suppress the phenotypic consequences of existing genetic polymorphisms [5], [6], affect epigenetically inherited phenotypes [7], and facilitate the spread of novel mutations [8].
Work in the agouti mouse model has confirmed that environmental alterations during pregnancy (most prominently in diet) affect epigenetically determined phenotypes in offspring, reportedly through the altered methylation status of intracisternal A-particle (IAP) retrotransposons upstream of the agouti locus (Waterland and Jirtle 2003; Wolff et al. 1998).
As discussed earlier, the maternal exposure to epigenetic modifiers can affect the transmission of epigenetically controlled traits.
It is tempting to speculate that the corresponding temperature changes in wheat could also epigenetically prime plants, affecting later stages of defence, as seen in UC1041.
In the case of histone methylation, there are no reports that explain or suggest either the somaclonal variation or the genes affected epigenetically.
These observations beg the question of whether the return trip through the transient, epigenetically unstable state affects (resets) the age program in isolation; the developmental program remains unchanged because the cells gravitate back to the 'ground-state' upon removal of the 'reprogramming factors' (Fig. 2a,b).
A different role of Trop-2 in cancer growth has been recently reported by Lin et al. [ 52] in lung carcinoma, where Trop-2 is epigenetically downregulated and affected by LOH, resulting in cancer progression via activation of IGF-1R signalling.
