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Seven cases (3%) showed B-Raf mutation but none of these had a coincidental mutation in the K-Ras gene nor a statistical association with the other clinico-pathological variables.
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Here we restricted ourselves to shared indels larger than three nucleotides to ensure a certain level of complexity in the sequences, so that they would not be confused with coincidental random mutations.
In conclusion, this analysis provided to detect some molecular differences between primary metastatic and nonmetastatic CRCs, with K-Ras and p16INK4A statistically altered in metastatic tumours; particular gene combinations, such as coincidental K-Ras mutation with two methylated genes are associated to a metastogenic phenotype.
This study also pointed to patterns of coincidental and exclusive mutations.
E-Cadherin promoter methylation was prevalent in the right colon (univariate analysis P=0.011; multivariate analysis P=0.007), so that coincidental K-Ras mutations and E-Cadherin methylation frequently occurred in proximal (27%) rather than left colon (5%) and rectum (8%) (P<0.001).
For example, the newly identified IDH1 mutation was often coincidental with TP53 mutations (83% of cases compared with 27% in patients with wild-type IDH1) and negatively correlated with the presence of PTEN, RB1, EGFR or NF1 mutations (0% of cases compared with 60% in patients with wild-type IDH1), suggesting fundamentally different cancers at the molecular level.
The combination of mapping results by Mahama and Palmer (2003) and Zabala and Vodkin (2007) revealed the coincidental mapping of y11, another chlorophyll deficient mutant to the same chromosome arm as the mutation in MinnGold, and led us to consider that y11 may also be caused by a mutation in Glyma13g30560.
Nevertheless, it is possible that the mapping of these mutations onto the crystal structure is coincidental.
These FV-GV correlations were not likely to be coincidental because they were maintained in the presence of a KCNQ1 mutation, R243Q, that shifted the voltage dependence of channel opening but did not change the correlation of the GV to Fmain or Fhigh in the absence or precense of RKK/EEE KCNE1, respectively.
We investigated whether this order was coincidental or caused by epistasis, by investigating the phenotypes of mutations in these three genes, in different combinations, in a bem1∆ background.
Chiang et al (2004) also demonstrated that the three key mutations (APC, K-Ras and p53) are rarely coincidental in 122 sporadic CRCs.
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