Gene Mutations are Not Fungible: "How Mutations in a Specific Gene Cause Different Types of Disease"

For persons interested in cancer litigation and genetic causes of cancers, a key point to learn and apply is that gene mutations are not fungible. Nonetheless, I often hear people refer to mutations as if there is only one type of mutation per gene, or as if different mutations all have the same impact. To the contrary, there are hundreds or thousands of different mutations of some genes, and the impacts vary. Some mutations are pathogenic, some are benign, and some are "variants of unknown significance," commonly referred to as a VUS.

The fact that mutations are not fungible leads to a question: how to explore and understand the impact of a particular mutation? Multiple research methods can be used to seek out answers to those questions. A recent example illustrates the point.

Researchers in the UK were seeking to better understand the significance of different mutations in RUNX1, a gene known for its role in some blood cancers. To that end, they undertook in vitro experiments with cells and found that different mutations produced different outcomes, as explained in a January 14, 2021 article at Medical Express. The article explained as follows:

"Co-corresponding author Dr. Sophie Kellaway said: "We used a cell culture system capable of generating blood cells in vitro, then induced the mutant forms of RUNX1 in these cells and immediately examined the effect on cellular behavior and gene activity.

"We found that every RUNX1 mutation changed cells in a different way and had a different impact on how genes responded.

"What we have been able to demonstrate is that different genetic alterations in RUNX1 can send cells towards alternate paths of malignancy."

The full scientific article is open access; it is: Sophie G Kellaway et al, Different mutant RUNX1 oncoproteins program alternate haematopoietic differentiation trajectories, Life Science Alliance (2021). DOI: 10.26508/lsa.202000864

In sum, mutations are not fungible. And, it appears further research will help to reveal why a person with mutation A develops cancer type #1, as opposed to mutation B causing cancer type #2.