The genetic changes in 11p15.5-related pheochromocytomas and paragangliomas

Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors. The development of these tumors is associated with more than 20 genes. The aforementioned genes are subdivided into three clusters. The pseudohypoxic, kinase-signaling and Wnt clusters. The pseudohypoxic cluster is the only one that has been demonstrated to be associated with DNA methylation changes, including alterations in the 11p15.5 region. The objective of this study was to identify alterations in the 11p15.5 region, ascertain their prevalence in PPGLs, and subsequently compare them with the genomic and somatic mutations that cluster PPGLs. One hundred and fifty tumor samples were subjected to analysis. A total of 90 cases (60%) exhibited no alterations in the 11p15.5 region. The most prevalent alterations were maternal allele loss, observed in 45 cases (30%), pUPD (paternal uniparental disomy) in five cases (3.33%), and paternal allele gain in four cases (2.67%). The data presented here suggest that two mechanisms may be involved in the formation of PPGLs. These are reduced expression of CDKN1C (maternal allele deletion) and overexpression of IGF2 (pUPD, paternal allele gain). A statistically significant difference was observed in the frequency of alterations in the 11p15.5 region when comparing cluster 1 and cluster 2 (P-value <0.0001). This study is the first to describe pUPD and paternal allele gain as somatic alterations in PPGLs. In addition, our findings indicate that alterations in the 11p15.5 region are not exclusive to cluster 1. Consequently, the alterations in the 11p15.5 region cannot be regarded as a marker for cluster 1.