Expression and somatic mutations of SDHAF2 (SDH5), a novel endocrine tumor suppressor gene in parathyroid tumors of primary hyperparathyroidism.
To investigate the SDHAF2 gene and its effect on primary hyperparathyroidism. Parathyroid tumors causing primary hyperparathyroidism (pHPT) are one of the more common endocrine neoplasias. Loss of heterozygosity at chromosome 11q13 is the most common chromosomal aberration in parathyroid tumors occurring in about 40% of sporadic tumors. Only 15-19% display somatic mutations in the MEN1 gene, which suggest that this chromosomal region may harbor additional genes of importance in parathyroid tumor development. The SDHAF2 (formerly SDH5) gene is a recently identified neuroendocrine tumor suppressor gene at this locus, and inherited mutations of the SDHAF2 gene has been linked to familial paraganglioma. We demonstrate that the SDHAF2 gene is expressed in parathyroid tissue using RT-PCR. Because detection of inactivating mutations is the major criterion for validating a candidate tumor suppressor, we used automated sequencing of the coding region and intron/exon boundaries in 80 sporadic parathyroid adenomas from patients with pHPT. A known polymorphisms (A to G substitution; rs879647) was identified in 9/80 parathyroid tumors but no tumor-specific somatic mutational aberrations, such as nonsense, frameshift, or other inactivating mutations were identified. The SDHAF2 gene is expressed in parathyroid tissue. However, somatic mutations of the SDHAF2 tumor suppressor gene are unlikely to frequently contribute to parathyroid tumor development in sporadic pHPT.
Department of Surgery, Yale University School of Medicine, 333 Cedar Street, TMP202, Box 208062, New Haven, CT 06520, USA.
Lee F
LF
Starker
Alberto
A
Delgado-Verdugo
Robert
R
Udelsman
Peyman
P
Björklund
Tobias
T
Carling
D000368:Aged; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006801:Humans; D049950:Hyperparathyroidism, Primary / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics*; D009154:Mutation; D018358:Neuroendocrine Tumors / Q000150:complications / Q000235:genetics*; D010282:Parathyroid Neoplasms / Q000150:complications / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
D024101:Mitochondrial Proteins; C543341:SDHAF2 protein, human