Mutant Allele Imbalance in Cancer

The search for somatic mutations that drive the initiation and progression of human tumors has dominated recent cancer research. While much emphasis has been placed on characterizing the prevalence and function of driver mutations, comparatively less is known about their serial genetic evolution. Indeed, study of this phenomenon has largely focused on tumor-suppressor genes recessive at the cellular level or mechanisms of resistance in tumors with mutant oncogenes targeted by therapy. There is, however, a growing appreciation that despite a decades-old presumption of heterozygosity, changes in mutant oncogene zygosity are common and drive dosage and stoichiometry changes that lead to selective growth advantages. Here, we review the recent progress in understanding mutant allele imbalance and its implications for tumor biology, cancer evolution, and response to anticancer therapy.

Automated summary

The search for somatic mutations that drive human tumors has been a focus in recent cancer research, with less emphasis on understanding the serial genetic evolution of driver mutations. Changes in mutant oncogene zygosity are common and can lead to selective growth advantages. Further research is needed to fully understand the implications of mutant allele imbalance in tumor biology, cancer evolution, and response to anticancer therapy.