Role of NF2 Mutation in the Development of Eleven Different Cancers

Background/Objectives: With the rise in prevalence of diagnostic genetic techniques like RNA sequencing and whole exome sequencing (WES), as well as biological treatment regiments for cancer therapy, several genes have been implicated in carcinogenesis. This review aims to update our understanding of the Neurofibromatosis 2 (NF2) gene and its role in the pathogenesis of various cancers. Methods: A comprehensive search of five online databases yielded 43 studies that highlighted the effect of sporadic NF2 mutations on several cancers, including sporadic meningioma, ependymoma, schwannoma, mesothelioma, breast cancer, hepatocellular carcinoma, prostate cancer, glioblastoma, thyroid cancer, and melanoma. Of note were key biological pathways implicated in cancer formation resulting from sporadic NF2 mutations. Results: NF2 gene mutations are implicated in over 11 different cancers, including several CNS tumors, soli-organ tumors, and skin cancer. NF2 acts as a driver mutation in some cancers, as a non-driver mutation in some cancers, and has simple associated mutations with other cancers. In terms of biological pathway involvement, 8 of the 11 cancers with NF2 mutations show evidence of Hippo signaling cascade involvement. Conclusions: Several cancers characterized by mutations in the NF2 gene have associations with the Hippo signaling pathway. However, future studies remain to be done to further elucidate the role of the Hippo signaling pathway in the carcinogenesis of human NF2-mutant tumors. The findings of this review provide insights into the role of NF2 mutations in cancers, Hippo signaling in NF2-mutant cancers, and current gaps in our knowledge regarding the two.