2. Academic Validation
  3. Updates on the genetics and the clinical impacts on phaeochromocytoma and paraganglioma in the new era

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.
Suja Pillai 1,  Vinod Gopalan 1,  Robert A Smith 2,  Alfred K-Y Lam 3
Affiliations

Affiliations

  • 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].
PMID: 26839173 DOI: 10.1016/j.critrevonc.2016.01.022
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.

Keywords

Immunohistochemistry; Mutations; Paraganglioma; Phaeochromocytoma; Sequencing.

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