Updates on the genetics and the clinical impacts on phaeochromocytoma and paraganglioma in the new era
- Crit Rev Oncol Hematol. 2016 Apr;100:190-208. doi: 10.1016/j.critrevonc.2016.01.022.
- 1. Cancer Molecular Pathology, School of Medicine and Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, Australia.
- 2. Cancer Molecular Pathology, School of Medicine and Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, Australia; Genomics Research Centre, Institute of Health and Biomedical Innovation, QueenslandUniversity of Technology, Queensland, Australia.
- 3. Cancer Molecular Pathology, School of Medicine and Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, Australia. Electronic address: [email protected].
Genetic mutations of phaeochromocytoma (PCC) and paraganglioma (PGL) are mainly classified into two major clusters. Cluster 1 mutations are involved with the pseudo hypoxic pathway and comprised of PHD2, VHL, SDHx, IDH, HIF2A, MDH2 and FH mutated PCC/PGL. Cluster 2 mutations are associated with abnormal activation of kinase signalling pathways and included mutations of RET, NF1, KIF1Bβ, MAX and TMEM127. In addition, VHL, SDHx (cluster 1 genes) and RET, NF1 (cluster 2 genes) germline mutations are involved in the neuronal precursor cell pathway in the pathogeneses of PCC/PGL. Also, GDNF, H-Ras, K-Ras, GNAS, CDKN2A (p16), p53, BAP1, BRCA1&2, ATRX and KMT2D mutations have roles in the development of PCC/PGLs. Overall, known genetic mutations account for the pathogenesis of approximately 60% of PCC/PGLs. Genetic mutations, pathological parameters and biochemical markers are used for better prediction of the outcome of patients with this group of tumours. Immunohistochemistry and gene Sequencing can ensure a more effective detection, prediction of malignant potential and treatment of PCC/PCLs.