TY - JOUR
T1 - Comment
T2 - Analysis of the SDHD gene, the susceptibility gene for familial paraganglioma syndrome (PGL1), in pheochromocytomas
AU - Aguiar, Ricardo C.T.
AU - Cox, Gerry
AU - Pomeroy, Scott L.
AU - Dahia, Patricia L.M.
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 2001
Y1 - 2001
N2 - Pheochromocytomas are neural crest-derived tumors that occur mostly sporadically, but may also be part of inherited syndromes. The molecular pathogenesis of sporadic pheochromocytomas remains unknown. Recently, the susceptibility gene for familial paraganglioma syndrome, a disorder embryologically related to pheochromocytomas, was characterized and shown to encode the small subunit of succinate dehydrogenase (SDHD), which is part of the mitochondrial complex II. This complex regulates oxygen-sensing signals. Importantly, hypoxic signals also appear to be related to the pathogenesis of pheochromocytomas associated with von Hippel-Lindau syndrome. We sequenced the entire coding region of the SDHD gene in a series of pheochromocytomas. Although we did not find mutations in the gene, we identified a new intronic single nucleotide polymorphism in 15% of the samples (g.97739A→G). We also confirmed the existence of a sequence highly homologous to the SDHD complementary DNA in chromosome 1p34-36, a region commonly deleted in pheochromocytomas. Full analysis of this sequence revealed a heterozygous single base substitution in 70% of our samples that was also present in the germline. This sequence does not appear to be transcribed and is probably a processed pseudogene. Therefore, despite its chromosomal location, it is unlikely that this sequence is a target of loss of heterozygosity in pheochromocytomas. In conclusion, mutations of the SDHD gene are not a common event in this series of sporadic pheochromocytomas. The existence of SDHD pseudogenes should be considered when analyzing complementary DNA-based samples.
AB - Pheochromocytomas are neural crest-derived tumors that occur mostly sporadically, but may also be part of inherited syndromes. The molecular pathogenesis of sporadic pheochromocytomas remains unknown. Recently, the susceptibility gene for familial paraganglioma syndrome, a disorder embryologically related to pheochromocytomas, was characterized and shown to encode the small subunit of succinate dehydrogenase (SDHD), which is part of the mitochondrial complex II. This complex regulates oxygen-sensing signals. Importantly, hypoxic signals also appear to be related to the pathogenesis of pheochromocytomas associated with von Hippel-Lindau syndrome. We sequenced the entire coding region of the SDHD gene in a series of pheochromocytomas. Although we did not find mutations in the gene, we identified a new intronic single nucleotide polymorphism in 15% of the samples (g.97739A→G). We also confirmed the existence of a sequence highly homologous to the SDHD complementary DNA in chromosome 1p34-36, a region commonly deleted in pheochromocytomas. Full analysis of this sequence revealed a heterozygous single base substitution in 70% of our samples that was also present in the germline. This sequence does not appear to be transcribed and is probably a processed pseudogene. Therefore, despite its chromosomal location, it is unlikely that this sequence is a target of loss of heterozygosity in pheochromocytomas. In conclusion, mutations of the SDHD gene are not a common event in this series of sporadic pheochromocytomas. The existence of SDHD pseudogenes should be considered when analyzing complementary DNA-based samples.
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U2 - 10.1210/jc.86.6.2890
DO - 10.1210/jc.86.6.2890
M3 - Review article
C2 - 11397905
AN - SCOPUS:0034977649
SN - 0021-972X
VL - 86
SP - 2890
EP - 2894
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 6
ER -