Reshma Pandit1, Kranti Khadilkar2, Vijaya Sarathi3, Rajeev Kasaliwal4, Manjunath Goroshi2, Shruti Khare2, Sandhya Nair2, Vijaya Raghavan2, Abhay Dalvi5, Priya Hira6, Gwendolyn Fernandes7, Pragati Sathe7, Amey Rojekar7, Gaurav Malhotra8, Ganesh Bakshi9, Gagan Prakash9, Anil Bhansali10, Rama Walia10, Sadishkumar Kamalanathan11, Jayaprakash Sahoo11, Ankush Desai12, Nikhil Bhagwat13, Prashanth Mappa14, Rajesh Rajput15, Sudha Rao Chandrashekhar16, Vyankatesh Shivane2, Padma Menon2, Anurag Lila2, Tushar Bandgar2, Nalini Shah2. 1. Department of EndocrinologySeth G S Medical College and KEM Hospital, Mumbai, Maharashtra, India reshmap9@gmail.com. 2. Department of EndocrinologySeth G S Medical College and KEM Hospital, Mumbai, Maharashtra, India. 3. Department of EndocrinologyVydehi Institute of Medical Sciences and Research Centre, Bangalore, Karnataka, India. 4. Department of EndocrinologyMahatma Gandhi Hospital and Medical College, Jaipur, Rajasthan, India. 5. Departments of General Surgery. 6. Radiology. 7. PathologySeth G S Medical College and KEM Hospital, Mumbai, Maharashtra, India. 8. Radiation Medicine CentreBhabha Atomic Research Centre, Mumbai, Maharashtra, India. 9. Department of Uro-oncologyTata Memorial Hospital, Mumbai, Maharashtra, India. 10. Department of EndocrinologyPostgraduate Institute of Medical Education & Research (PGIMER), Chandigarh, India. 11. Department of EndocrinologyJawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Pondicherry, India. 12. Endocrine UnitDepartment of Medicine, Goa Medical College, Bambolim, Goa, India. 13. Department of EndocrinologyTopiwala National Medical College & BYL Nair Charitable Hospital, Mumbai, Maharashtra, India. 14. Department of MedicineKannur Medical College and Hospital, Kannur, Kerala, India. 15. Department of EndocrinologyPt. B.D. Sharma PGIMS, Rohtak, Haryana, India. 16. Division of Pediatric EndocrinologyBai Jerbai Wadia Hospital for Children, Mumbai, Maharashtra, India.
Abstract
BACKGROUND: Genetic aetiology of pheochromocytoma (PCC) and paraganglioma (PGL) is increasingly being studied; however, Asian Indian data on this aspect are scarce. OBJECTIVE: To study the prevalence of germline mutations and genotype-phenotype correlation in Asian Indian PCC/PGL patients. DESIGN: In this study, 150 index patients (M:F, 73:77) with PCC/PGL were evaluated. Phenotypic data were collected. Germline mutations in five susceptibility genes (RET, VHL, SDHB, SDHD and SDHC) were tested by sequencing and NF1 was diagnosed according to phenotype. RESULT: Of the total population, 49 (32.7%) PCC/PGL patients had germline mutations (VHL: 23 (15.3%), RET: 13 (8.7%), SDHB: 9 (6%), SDHD: 2 (1.3%) and NF1: 2 (1.3%)). Amongst the 30 patients with familial and/or syndromic presentation, all had germline mutations (VHL: 14 (46.7%), RET: 13 (43.3%), SDHB: 1 (3.3%) and NF1: 2 (6.7%)). Out of 120 patients with apparently sporadic presentation, 19 (15.8%) had a germline mutation (VHL: 9 (7.5%), SDHB: 8 (6.7%) and SDHD: 2 (1.7%)). Mutation carriers were younger (29.9 ± 14.5 years vs 36.8 ± 14.9; P = 0.01) and had a higher prevalence of bilateral PCC (26.5% vs 2.9%, P < 0.001) and multifocal tumours (12.2% vs 0.96%, P = 0.06). Based on syndromic features, metastasis, location and number of tumours, around 96% mutations in our cohort could be detected by appropriately selected single gene testing. CONCLUSION: Asian Indians with PCC/PGL differ from Western cohorts in having preponderance of VHL mutations in multifocal tumours and apparently sporadic unilateral PCC. Syndromic presentation, metastasis, location and number of PCC/PGL can be effectively used for guiding genetic prioritisation.
BACKGROUND: Genetic aetiology of pheochromocytoma (PCC) and paraganglioma (PGL) is increasingly being studied; however, Asian Indian data on this aspect are scarce. OBJECTIVE: To study the prevalence of germline mutations and genotype-phenotype correlation in Asian Indian PCC/PGL patients. DESIGN: In this study, 150 index patients (M:F, 73:77) with PCC/PGL were evaluated. Phenotypic data were collected. Germline mutations in five susceptibility genes (RET, VHL, SDHB, SDHD and SDHC) were tested by sequencing and NF1 was diagnosed according to phenotype. RESULT: Of the total population, 49 (32.7%) PCC/PGL patients had germline mutations (VHL: 23 (15.3%), RET: 13 (8.7%), SDHB: 9 (6%), SDHD: 2 (1.3%) and NF1: 2 (1.3%)). Amongst the 30 patients with familial and/or syndromic presentation, all had germline mutations (VHL: 14 (46.7%), RET: 13 (43.3%), SDHB: 1 (3.3%) and NF1: 2 (6.7%)). Out of 120 patients with apparently sporadic presentation, 19 (15.8%) had a germline mutation (VHL: 9 (7.5%), SDHB: 8 (6.7%) and SDHD: 2 (1.7%)). Mutation carriers were younger (29.9 ± 14.5 years vs 36.8 ± 14.9; P = 0.01) and had a higher prevalence of bilateral PCC (26.5% vs 2.9%, P < 0.001) and multifocal tumours (12.2% vs 0.96%, P = 0.06). Based on syndromic features, metastasis, location and number of tumours, around 96% mutations in our cohort could be detected by appropriately selected single gene testing. CONCLUSION: Asian Indians with PCC/PGL differ from Western cohorts in having preponderance of VHL mutations in multifocal tumours and apparently sporadic unilateral PCC. Syndromic presentation, metastasis, location and number of PCC/PGL can be effectively used for guiding genetic prioritisation.
Authors: Mei Yin Wong; Katrina A Andrews; Benjamin G Challis; Soo-Mi Park; Carlo L Acerini; Eamonn R Maher; Ruth T Casey Journal: Clin Endocrinol (Oxf) Date: 2019-01-29 Impact factor: 3.478
Authors: Shatha Albattal; Meshael Alswailem; Yosra Moria; Hindi Al-Hindi; Majed Dasouki; Mohamed Abouelhoda; Hala Aba Alkhail; Entissar Alsuhaibani; Ali S Alzahrani Journal: Oncotarget Date: 2019-10-15