Moreover, the three PRO mutations appearing in the table are among those most involved in cross-resistance within the PI class and the RT mutations listed in the same table comprise the thymidine analog mutations well known to mediate cross-resistance to all the NRTIs, (see, e.g. Gallant et al., 2003).
The Y253 and E255V mutations are well known P-loop mutations causing resistance to imatinib and nilotinib while sensitive to dasatinib when either found individually or in the same molecule [ 5].
In light of this theory, the result that deleterious mutations reduce the probability of fixation for beneficial mutations is well known.
One of these mutations is well known: Nearly 30percentt of the population has one copy, and nine percent has two copies.
The variability of the natural history and prognosis as a function of different ATP1A2 mutations are well known.
IDH1 and IDH2 mutations are well known in gliomas [ 6], but are notoriously difficult to grow in culture [ 7].
Despite the fact that maternal effect mutations are well known in lower organisms, only a few examples have been reported in mammals.
The remaining mutations are well known due to their involvement in the PI3K/PTEN/AKT/mTOR [ 35] and the Ras/Raf/MEK/ERK [ 36] pathways.
As EGFR mutations are well known to constitutively activate ERK causing cancer, we decided to generate a new model of the EGF activated ERK pathway which would correctly predict the effects of various cancerous alterations and enable further investigations.
The high clinical variability in patients carrying different POLG mutations is well known and has been illustrated in numerous publications during the past 10 years (Van Goethem et al., 2001, 2003, 2004; Luoma et al., 2004; Naviaux and Nguyen, 2004; Horvath et al., 2006; Chinnery and Zeviani, 2008).
