| http://purl.uniprot.org/citations/18678321 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18678321 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18678321 | http://www.w3.org/2000/01/rdf-schema#comment | "Individuals with PTEN mutations have Cowden syndrome (CS), associated with breast, thyroid, and endometrial neoplasias. Many more patients with features of CS, not meeting diagnostic criteria (termed CS-like), are evaluated by clinicians for CS-related cancer risk. Germline mutations in succinate dehydrogenase subunits SDHB-D cause pheochromocytoma-paraganglioma syndrome. One to five percent of SDHB/SDHD mutation carriers have renal cell or papillary thyroid carcinomas, which are also CS-related features. SDHB-D may be candidate susceptibility genes for some PTEN mutation-negative individuals with CS-like cancers. To address this hypothesis, germline SDHB-D mutation analysis in 375 PTEN mutation-negative CS/CS-like individuals was performed, followed by functional analysis of identified SDH mutations/variants. Of 375 PTEN mutation-negative CS/CS-like individuals, 74 (20%) had increased manganese superoxide dismutase (MnSOD) expression, a manifestation of mitochondrial dysfunction. Among these, 10 (13.5%) had germline mutations/variants in SDHB (n = 3) or SDHD (7), not found in 700 controls (p < 0.001). Compared to PTEN mutation-positive CS/CS-like individuals, those with SDH mutations/variants were enriched for carcinomas of the female breast (6/9 SDH versus 30/107 PTEN, p < 0.001), thyroid (5/10 versus 15/106, p < 0.001), and kidney (2/10 versus 4/230, p = 0.026). In the absence of PTEN alteration, CS/CS-like-related SDH mutations/variants show increased phosphorylation of AKT and/or MAPK, downstream manifestations of PTEN dysfunction. Germline SDH mutations/variants occur in a subset of PTEN mutation-negative CS/CS-like individuals and are associated with increased frequencies of breast, thyroid, and renal cancers beyond those conferred by germline PTEN mutations. SDH testing should be considered for germline PTEN mutation-negative CS/CS-like individuals, especially in the setting of breast, thyroid, and/or renal cancers."xsd:string |
| http://purl.uniprot.org/citations/18678321 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.ajhg.2008.07.011"xsd:string |
| http://purl.uniprot.org/citations/18678321 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.ajhg.2008.07.011"xsd:string |
| http://purl.uniprot.org/citations/18678321 | http://purl.uniprot.org/core/author | "Eng C."xsd:string |
| http://purl.uniprot.org/citations/18678321 | http://purl.uniprot.org/core/author | "Eng C."xsd:string |
| http://purl.uniprot.org/citations/18678321 | http://purl.uniprot.org/core/author | "Ni Y."xsd:string |
| http://purl.uniprot.org/citations/18678321 | http://purl.uniprot.org/core/author | "Ni Y."xsd:string |
| http://purl.uniprot.org/citations/18678321 | http://purl.uniprot.org/core/author | "Orloff M.S."xsd:string |
| http://purl.uniprot.org/citations/18678321 | http://purl.uniprot.org/core/author | "Orloff M.S."xsd:string |
| http://purl.uniprot.org/citations/18678321 | http://purl.uniprot.org/core/author | "Patocs A."xsd:string |
| http://purl.uniprot.org/citations/18678321 | http://purl.uniprot.org/core/author | "Patocs A."xsd:string |
| http://purl.uniprot.org/citations/18678321 | http://purl.uniprot.org/core/author | "Edelman E."xsd:string |
| http://purl.uniprot.org/citations/18678321 | http://purl.uniprot.org/core/author | "Edelman E."xsd:string |
| http://purl.uniprot.org/citations/18678321 | http://purl.uniprot.org/core/author | "Lobo G."xsd:string |
| http://purl.uniprot.org/citations/18678321 | http://purl.uniprot.org/core/author | "Lobo G."xsd:string |
| http://purl.uniprot.org/citations/18678321 | http://purl.uniprot.org/core/author | "Platzer P."xsd:string |
| http://purl.uniprot.org/citations/18678321 | http://purl.uniprot.org/core/author | "Platzer P."xsd:string |
| http://purl.uniprot.org/citations/18678321 | http://purl.uniprot.org/core/author | "Sadler T."xsd:string |
| http://purl.uniprot.org/citations/18678321 | http://purl.uniprot.org/core/author | "Sadler T."xsd:string |
| http://purl.uniprot.org/citations/18678321 | http://purl.uniprot.org/core/author | "Waite K.A."xsd:string |
| http://purl.uniprot.org/citations/18678321 | http://purl.uniprot.org/core/author | "Waite K.A."xsd:string |
| http://purl.uniprot.org/citations/18678321 | http://purl.uniprot.org/core/author | "Zbuk K.M."xsd:string |
| http://purl.uniprot.org/citations/18678321 | http://purl.uniprot.org/core/author | "Zbuk K.M."xsd:string |