Inactivating mutations of the neurofibromatosis type 2 (NF2) tumor suppressor gene merlin have been described in nearly 60% of primary malignant mesothelioma and in approximately 20% of the mesothelioma cell lines.
Consequently, the disruptions due to merlin inactivation in the progression of malignant mesothelioma may represent a tumor suppressor role operating by a different pathway than that in schwannoma or meningioma.
Nearly 75% of MM cases have inactivating mutations in the NF2 (neurofibromatosis type 2; Merlin) gene or in downstream signaling molecules of the Hippo signaling cascade, which negatively regulates the transcription factor Yes-associated protein (YAP).
MM is a very aggressive tumor associated with asbestos exposure, and genetic alterations in <i>NF2</i> that abrogate merlin's functional activity are found in about 40% of MMs, indicating the importance of <i>NF2</i> inactivation in MM development and progression.
Collectively, these findings suggest that merlin inactivation is a critical step in MM pathogenesis and is related, at least in part, with upregulation of FAK activity.
Interestingly, biallelic NF2 gene inactivation is one of the most common mutations associated with the development of malignant mesothelioma (MM), a highly fatal malignancy that arises in the pleura and less frequently in the pericardium, peritoneum, and tunica vaginalis.
To study if LOH of the NF2 gene is a consistent feature in MM, we performed a more detailed analysis of chromosome 22q that included a NF2 marker (NF2CA3).