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Although many genetic risk factors for neurodevelopmental disorders have been identified, few single-gene mutations are alone sufficient to cause the disorder.
However, long-term colony-forming assays and in vivo murine models have failed to show that PIG-A mutations are alone sufficient to drive clonal expansion.
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This hypothesis was based on the observations from genetic mouse models of serrated neoplasia in which the BRAF V600E mutation or activating KRAS mutation was alone sufficient to induce serrated neoplasia in the long-term; however, in the short-term, OIS barriers prevented rapid tumorigenesis.
Further, we show that BRAF mutations occur in association with CIMP phenotype in colorectal serrated polyps while KRAS mutations are found alone.
TET2, ASXL1, IDH1/2, and EZH2 gene mutations are found alone or in combination with JAK2 or MPL mutations and influence the epigenetic regulation of transcription resulting in the possible silencing of putative tumor suppressor genes in MPNs.
The papers in question both suggest that instead of analyzing the effects of cancer-promoting mutations in the context of an entirely mutant animal or tissue, it would be more informative to generate mosaic animals in which cancer-disposing mutations are introduced, either alone or in specific combinations, in only a subset of cells.
Each of these mutations was beneficial alone, but the double mutant was no more fit than the besAE2 single mutant.
D101 was mutated to alanine, R166 to serine, D153 to alanine, K328 to alanine, and the Mg2+ ion ligand E322 to tyrosine to prevent the Mg2+ from binding in the active site; these mutations were made alone and in combination.
In sharp contrast to COS7 and 661W cells, co-expression of RPGRIP1α1 with RPGR1 19 or RPGRORF15 in Hep3B cells did not lead to remarkable differences in their co-localization regardless of whether disease mutations were expressed alone in either partner or together in both partners (supplementary material Fig. S10).
Although p53 mutations are present almost exclusively in poorly differentiated thyroid tumours (Wynford-Thomas, 1997), p53 mutation alone is not sufficient to drive progression of thyroid cancer to the aggressive anaplastic form (Wyllie et al, 1999).
A cancer is 'nongenetic' (sporadic) in origin when the set of cancer-causing mutations are due to somatic mutation alone.
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