Kay Reen Ting1, Pei Yi Ong1, Samuel Ow Guan Wei1,2, Rajeev Parameswaran3, Chin Meng Khoo2,4, Doddabele Srinivasa Deepak4, Soo-Chin Lee5,6. 1. Department of Haematology-Oncology, National University Cancer Institute, Singapore (NCIS), National University Health System, 1E Kent Ridge Road, Singapore, 119228, Singapore. 2. Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. 3. Department of Surgery, Division of General Surgery (Thyroid and Endocrine Surgery), National University Hospital, Singapore, Singapore. 4. Department of Medicine, Division of Endocrinology, National University Hospital, Singapore, Singapore. 5. Department of Haematology-Oncology, National University Cancer Institute, Singapore (NCIS), National University Health System, 1E Kent Ridge Road, Singapore, 119228, Singapore. csilsc@nus.edu.sg. 6. Cancer Science Institute, Singapore, Singapore. csilsc@nus.edu.sg.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Authors: R Pai; A Ebenazer; M J Paul; N Thomas; A Nair; M S Seshadri; R Oommen; N Shanthly; A Devasia; G Rebekah; L Jeyaseelan; S Rajaratnam Journal: Horm Metab Res Date: 2014-06-30 Impact factor: 2.936