Sotillo, E. et al. Convergence of acquired mutations and alternative splicing of CD19 enables resistance to CART-19 immunotherapy.
Four additional Dutch subjects of whom exonic sequence data were available, including two patients with severe 5FU toxicity, a son of a patient with lethal toxicity and a healthy volunteer who was coincidently found to have a DPD deficiency during another study were further investigated for intronic mutations and alternative splicing.
So far, a number of resistance mechanisms have been identified, including secondary NRAS mutations and BRAF alternative splicing, leading to reactivation of the MAPK pathway.
In addition, this comprehensive study analyzed the clinical features and prognostic impact of mutations and suggested alternative risk stratification of AML patients by inclusion of DNMT3A, MLL-PTD and TP53 genes in the proposed European Leukemia Net (ELN) system [ 35, 36].
For instance, DDIs have been used to gain a better understanding of protein networks [2], for predicting the effects of mutations [3] and alternative splicing events that effect interacting domains [4], for developing drugs to inhibit pathological protein interactions [5], [6], and for designing novel protein interactions [7].
Frame shift mutations and use of alternative reading frames have been described for HRSV (35 – 35 ).
Furthermore, the repertoire of cancer models suitable for use with the screening platform can be custom designed through combining various oncogenic and tumour-suppressor mutations, and by using alternative drivers to induce tumours in different tissues.
There is a close relationship between the CFTR genotype and the pancreatic phenotype, revealing "severe" mutations (eg, F508del, all class 1 mutations) to be associated with pancreatic insufficiency and "mild" mutations, such as a series of missense and alternative splice mutations, to be associated with pancreatic sufficiency.
As observed among mRNA sequences of their hosts, the main context-dependent mutations that reduced model error were those that eliminated CpG and UpA dinucleotides, prominently represented among both the first choice and alternative mutations.
Few studies have addressed AS variation among individuals within a species, although it has been noted that extensive AS variation in humans may underlie phenotypic diversity and disease susceptibility [ 7], and mutations affecting alternative splicing can play a role in disease [ 12].
Clusters E and F basically correlated negatively with sensitivity, included the indices of CAT2 (0 and 3 h), alternative oxidase mutation (TDNA- AOX1), and alternative oxidase antisense (AS- AOX).
