Characteristics and genetic testing outcomes of patients with clinically suspected paraganglioma/pheochromocytoma (PGL/PCC) syndrome in Singapore

• Published in: Hereditary cancer in clinical practice Vol. 18; no. 1; p. 24
• Main Authors: Ting, Kay Reen, Ong, Pei Yi, Wei, Samuel Ow Guan, Parameswaran, Rajeev, Khoo, Chin Meng, Deepak, Doddabele Srinivasa, Lee, Soo-Chin
• Format: Journal Article
• Language: English
• Published: Poland BioMed Central Ltd 11.12.2020; BioMed Central; BMC
• Subjects: Abdomen; Age; Analysis; Cancer; Chinese; Colorectal cancer; Family medical history; Gene deletion; Genes; Genetic aspects; Genetic counseling; Genetic screening; Genetic testing; Head and neck; Health counseling; Hereditary paraganglioma; Metastasis; Neck; Neuroendocrine tumors; Next-generation sequencing; Paraganglioma; Patients; Pheochromocytoma; SDHB; SDHD; Tumors; VHL protein; Singapore; Chinese; Pheochromocytoma; Genetic testing; SDHD; Hereditary paraganglioma; SDHB
• ISSN: 1731-2302; 1897-4287; 1897-4287
• DOI: 10.1186/s13053-020-00156-9

Hereditary paraganglioma (PGL) and pheochromocytoma (PCC) syndromes are rare conditions, with limited data on spectrum of causative gene variants of these syndromes in Asian patients. We describe the clinical characteristics and genetic testing outcomes of patients with suspected hereditary PGL/PCC who were referred to a tertiary cancer genetics clinic in Singapore. Among 2196 patients with suspected hereditary cancer syndrome evaluated at the cancer genetics clinic from 2000 to 2019, 13/2196 (0.6%) patients fulfilled clinical suspicion for hereditary PGL/PCC syndrome. After genetic counselling, 10 patients underwent multi-gene next generation sequencing and deletion/duplication analysis, including SDHAF2, SDHA, SDHB, SDHC, SDHD, VHL, NF1, RET, MAX, and TMEM127. Seven of 10 patients (70%) were identified to carry pathogenic variants, including 3 unrelated Chinese patients with head and neck PGL who carried the same SDHD: c.3G > C (p.Met1Ile) variant that was previously reported to be a possible founder variant in Chinese, and 3 patients with urogenital PGL and 1 patient with retroperitoneal PGL who carried different SDHB variants. Variant carriers were younger, more likely to present with multiple tumours, or have family history of paraganglioma or pheochromocytoma, than non- variant carriers. Hereditary PGL/PCC accounts for only 0.6% of patients seen in an adult cancer genetics clinic in Asia. SDHD and SDHB genes remain the most important causative genes of hereditary PGL/PCC in Asia even when patients are tested with multi-gene NGS panel.