We recently published a study in which we described a novel mutation in the phosphatidylinositol 3-kinase (PIK3CA) gene, which is involved in numerous cancers.1 During revision of the article, an interesting question of general interest in the area of molecular genetics arose.
The mutation frequency in our cohort was approximately 2% and we were asked if the mutation could in fact be a polymorphism rather than a mutation. In the search for a consensus definition of the term “polymorphism,” we discovered that any polymorphism is based on a mutation and that the frequency of the mutation needs to be between 1% and 10% of the investigated population, but there was no consensus definition for the term “polymorphism.” In turn, this observation means that a polymorphism is defined on the “gut feeling” of scientists rather than by hard scientific criteria. Moreover, there is no consensus regarding how large the population must be to identify a polymorphism as a polymorphism, thus leading to the problem that any mutation can become a rare polymorphism, provided the study cohort is large enough and the mutation is identified in “enough” individuals. In addition, a mutation or polymorphism could occur in both healthy individuals and those with cancer, but their frequencies may differ depending on the person's health status. Moreover, to the best of our knowledge, there is no information regarding to what extent a polymorphism may be based on the ethnic background of the study population; thus, a mutation in Asian patients may be a wild-type in a white population.
We believe that, in the area of genomics and personalized medicine, it is necessary to establish consensus definitions for the basic genetic terms that apply to all disciplines of molecular biology and that are accessible worldwide (eg, in the GenBank sequence database). Therefore, we would encourage harmonizing the definition of genetic terms.