Loss of maternal chromosome 11 is a signature event in SDHAF2, SDHD, and VHL-related paragangliomas, but less significant in SDHB-related paragangliomas.

摘要: // Attje S. Hoekstra 1 , Erik F. Hensen 2 Ekaterina Jordanova 3 Esther Korpershoek 4 Anouk N.A. van der Horst-Schrivers 5 Cees Cornelisse Eleonora P.M. Corssmit 6 Frederik J. Hes 7 Jeroen C. Jansen 8 Henricus Kunst 9 Henri J.L.M. Timmers 10 Adrian Bateman 11 Diana Eccles 12 Judith V.M.G. Bovee Peter Devilee 1, Jean-Pierre Bayley Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands Otolaryngology/Head and Neck Surgery, VU Amsterdam, Pathology, Josephine Nefkens Institute, Erasmus Center Rotterdam, Endocrinology, Groningen, Endocrinology Metabolic Diseases, Clinical Otorhinolaryngology, Head Radboud Centre, Nijmegen, Medicine, Division Cellular Hospital Southampton, UK Southampton School Cancer Sciences Division, Somers Research Building, Correspondence to: Bayley, email: J.P.L.Bayley@lumc.nl Devilee, P.Devilee@lumc.nl Keywords: paraganglioma, pheochromocytoma, succinate dehydrogenase, Von Hippel-Lindau, loss heterozygosity Received: September 06, 2016      Accepted: January 04, 2017      Published: 14, 2017 ABSTRACT Germline mutations in the dehydrogenase (SDHA, SDHB, SDHC, SDHD, SDHAF2) or Hippel-Lindau (VHL) genes cause hereditary paraganglioma/pheochromocytoma. While SDHB (1p36) VHL (3p25) are associated with autosomal dominant disease, SDHD (11q23) SDHAF2 (11q13) show a remarkable parent-of-origin effect whereby tumor formation is almost completely dependent on paternal transmission mutant allele. Loss entire maternal copy chromosome occurs frequently -linked tumors, has been suggested to be basis for this typical inheritance pattern. Using fluorescent situ hybridization, microsatellite marker SNP array analysis, we demonstrate that also frequent -related PGLs, occurring 89% tumors. Analysis two imprinted differentially methylated regions (DMR) 11p15, H19-DMR KvDMR, showed always affected 11. Likewise, 11p15 was demonstrated 85% 75% PGLs/PCCs. By contrast, both copies were found retained 62% -mutated PGLs/PCCs, while only 31% 11p15. Genome-wide number analysis revealed 1p tumors greater genomic instability compared . These results highly specific statistically significant event but less suggesting these have distinct genetic etiology.