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

Pheochromocytomas and paragangliomas are neuroendocrine tumors. The development of these tumors is associated with more than 20 genes. These genes are divided into 3 clusters: pseudohypoxic, kinase-signaling, and Wnt. The pseudohypoxic cluster is the only one that is associated with DNA methylation changes, including changes in the 11p15.5 region. The aim of this study was to identify changes in the 11p15.5 region and their frequency in pheochromocytomas and paragangliomas. And compare with genomic and somatic mutations that cluster pheochromocytomas and paragangliomas. To identify alterations in the 11p15.5 region, we used the MS-MLPA technique. The results of this assay were then compared with those obtained from the SNP array (850k, Illumina). 150 samples were examined by both techniques. A total of 90 cases (60%) exhibited no alterations in the 11p15.5 region. The most common changes were maternal allele loss in 45 cases (30%), pUPD in 5 cases (3.33%) and paternal allele gain in 4 cases (2.67%). 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). We found that there are other alternations in the 11p15.5 region in pheochromocytomas and paragangliomas in addition to the previously described deletion of the maternal allele. This study is the first to describe pUPD and paternal allele gain in pheochromocytomas and paragangliomas. We also show that alterations in the 11p15.5 region are not unique to cluster 1.