title: Updates on the genetics and the clinical impacts on phaeochromocytoma and paraganglioma in the new era.
abstract: 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.
authors.affiliation: Cancer Molecular Pathology, School of Medicine and Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, Australia.
authors.forename: Suja
authors.initials: S
authors.lastname: Pillai
authors.affiliation: Cancer Molecular Pathology, School of Medicine and Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, Australia.
authors.forename: Vinod
authors.initials: V
authors.lastname: Gopalan
authors.affiliation: 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.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Smith
authors.affiliation: Cancer Molecular Pathology, School of Medicine and Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, Australia. Electronic address: a.lam@griffith.edu.au.
authors.forename: Alfred K-Y
authors.initials: AK
authors.lastname: Lam
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry; D010235:Paraganglioma / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism; D010673:Pheochromocytoma / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor
keywords: Immunohistochemistry; Mutations; Paraganglioma; Phaeochromocytoma; Sequencing