Individuals without CDH1 mutation should take clinical surveillance by EGD (oesophagogastroduodenoscopy), while the ones with CDH1 high risk missense mutations or truncating mutations was strongly recommended to take prophylactic gastrectomy and under close follow-up [ 8, 49].
Moreover, the finding of significant independent associations in both dominant and additive inheritance modes for the F-1 SNPs, and recessive and additive inheritance modes for the S-1 SNPs, means that the search for the causative mutation should take into account the possibility that a single copy may confer a functional effect.
Thus, optimization of therapeutic antisense oligonucleotides promoting exon skipping and preventing the incorporation of nonsense mutations in the mature dystrophin RNA should take into account both the complex crosstalk between ESEs, SR and pre-mRNA and potential exon/exon associations.
Of course if applicable, tumour-specific mutations should be taken into account in pharmacogenetic analyses as it is the case in non-small-cell lung cancer and in the use of inhibitors of EGFR.
Future design of a specific HNSCC panel should take into consideration important actionable mutations identified through the ongoing large scale sequencing efforts.
These findings indicate that CCMs with similar pathology can be caused by multiple mechanisms, and that treatment strategies should take into account the causative mutation.
Future work further clarifying how TRPM8 mutations impact the channel may provide better clues to which direction pharmacological approaches should take, activating or blocking channel function.
A more realistic tumor growth model should take resistance to drug, such as may occur through mutation, into account.
Thus, it should take at least a few generations for the effects of new mutations to accumulate.
For these genes, one should take into account the leader peptide sequences when examining the current mutation database.
