Thus, this PIGQ mutation seemed a very plausible candidate for causing OS in Patient 4. The patient died before we discovered this mutation so we were unable to obtain samples to test the effect of this homozygous mutation on PIGQ activity.
To a first approximation, these mutations seem to represent a uniform background of positive selection pressures that are consistently observed in any set of samples we have analyzed.
This specific pathogenic variant is clearly highly penetrant for the neurological 'plus' features and it does support our earlier observation that misssense GTPase OPA1 mutations seem to have a more potent deleterious impact, possibly via a dominant negative mechanism and increased mitochondrial DNA instability (Yu-Wai-Man et al., 2010; Yu-Wai-Man and Chinnery, 2012).
Although the data show a modest activity of these drugs as a single agent with a response rate of approximately 10%, patients with PIK3CA mutations seem to have a higher response rate than patients with wild-type PIK3CA.
Severely inactivating mutations seem to give a more severe phenotype than mildly inactivating mutations.
Unlike KRAS, p53 mutations seem to be a late event in the development of PanINs to PDAC 20, 28.
IDH1 mutations seem to have a significant role in glial tumours (Ducray et al, 2009; Hartmann et al, 2009).
Compared to NRAS/BRAF wild-type patients, those with NRAS mutations seem to have a worse prognosis.
NSCLC patients with EGFR mutations seem to have a favourable prognosis [ 11, 12] whereas those with KRAS mutations have poor prognosis [ 13- 19].
For this post-zygotic selection, genetic mechanisms resulting from low genetic diversity and fixation of deleterious mutations seem to be a more likely explanation than ecological factors.
