How can same-gene mutations promote both cancer and developmental disorders?

The question of how same-gene mutations can drive both cancer and neurodevelopmental disorders has been puzzling. It has also been puzzling why those with neurodevelopmental disorders have a high risk of cancer. Ras, MEK, PI3K, PTEN, and SHP2 are among the oncogenic proteins that can harbor mutations that encode diseases other than cancer. Understanding why some of their mutations can promote cancer, whereas others promote neurodevelopmental diseases, and why even the same mutations may promote both phenotypes, has important clinical ramifications. Here, we review the literature and address these tantalizing questions. We propose that cell type-specific expression of the mutant protein, and of other proteins in the respective pathway, timing of activation (during embryonic development or sporadic emergence), and the absolute number of molecules that the mutations activate, alone or in combination, are pivotal in determining the pathological phenotypes-cancer and (or) developmental disorders.

Automated summary

The question of how the same gene mutations can lead to both cancer and neurodevelopmental disorders has always been puzzling. This article reviews the literature and proposes that factors such as cell type-specific expression of the mutant protein, timing of activation, and the absolute number of molecules involved play key roles in determining the pathological phenotypes.