ASCO GU 2018: Germline Pathogenic Variants in Patients with Pheochromocytoma

San Francisco, CA ( Shirley Yao and colleagues presented their findings of germline pathologic variants in patients with pheochromocytoma at today’s poster session at GU ASCO 2018. Approximately 25% of pheochromocytomas have a hereditary basis, and germline variants in the SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127, MAX, VHL, FH, RET, MEN1, and NF1 genes have been associated with a predisposition to pheochromocytoma and paraganglioma. Multi-gene hereditary cancer panel testing for pheochromocytoma has become increasingly more common than single-gene testing algorithms. Identification of a pathogenic or likely pathogenic variant (PV/LPV) in one of these genes has important implications for surveillance in patients and their family members. The objective of this study was to describe the spectrum of PV/LPV variants identified in individuals with pheochromocytoma.

For this study, the authors performed a retrospective review of clinical and molecular data for all individuals diagnosed with pheochromocytoma who underwent panel testing through BioReference Laboratories from January 2016 – February 2017. Molecular data included at least SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127, MAX, VHL, FH, RET, MEN1, and NF1. With this search strategy, the authors identified 79 individuals that underwent testing due to a personal (n = 76) or family (n = 3) history of pheochromocytoma. The positive yield was 14% (11/79). The average age at tumor diagnosis was lower for patients testing positive for PV/LPV, than those who were negative (34 ± 14 years vs 44 years ± 16). The majority of PV/LPV were in SDHB (n = 4; 36%) mutations, followed by RET (n = 2, 18%), with the remaining variants being identified in SDHA (1), SDHC (1), VHL (1), TMEM127 (1), and MAX (1). Approximately half (6/11) of those with a PV/LPV had a non-syndromic presentation of a unilateral pheochromocytoma with no reported family history of pheochromocytoma or paraganglioma.

The authors concluded that their data support previous recommendations that patients with apparently sporadic, non-syndromic pheochromocytoma be considered for genetic testing. Using the molecular strategy described herein, panel testing is a useful tool for identifying individuals with hereditary pheochromocytoma.

Speaker: Shirley Yao, GeneDx, Inc., Gaithersburg, MD; GeneDx, Inc., Elmwood Park, NJ

Co-Authors: Elizabeth A Wiley, Lisa R. Susswein, Megan L. Marshall, Natalie J. Carter, Anna K. McGill, Rachel T. Klein, Ying Wang, Kathleen S. Hruska

Written by: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md, at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA