On the other hand, Figure 4 illustrates that it is very often that different genes in the same pathway are mutated in different samples, which not only explains why mutational gene signatures from different studies usually can't agree each other but also indicates the urgent needs for personal therapies.
Moreover, the used target gene sets all correspond to lists of genes that are mutated in different diseases without additionally available expression level data, i.e. they could not be analysed with microarray-specific gene set enrichment analysis techniques.
Of special interest is a spectrum of EGFR, ABL, MET, FLT3 and KIT cancer mutations that correspond to the same structurally conserved position in the activation loop, which appeared to be mutated in at least 8 different kinases (Figure 6A, Table S1).
Members of the Ras family of small GTPases are activated downstream of most growth factor receptor pathways and are found to be mutated in a number of different cancers (Schubbert et al., 2007).
NPHP1 is the product of a gene that is mutated in a different form of renal cystic disease, nephronophthisis (NPHP).
This result indicates that CCE5 is not allelic to BAK1, SERK4 or SERK5 and hence cce5 is mutated in a different gene.
Although homozygous mutations in loj or dl decrease adult viability, we did not observe additional, large effects when both genes are mutated in 2 different genetic backgrounds.
For example, we previously showed that different genes are mutated in cholangiocarcinomas from different geographical regions and with different etiologies [ 10, 11].
Because the experiment was performed with suspension cells, we cannot comment on whether both the target sites were mutated in the same cell or in different cells.
This discrepancy may have been due to different expression levels of AR in the DU145 and PC-3 cells lines as compared to LNCaP cells, the fact the AR receptor is mutated in LNCaP cells, or to different transfection efficiencies of the ebp1 plasmid among the three cell lines.
