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Utility of the succinate: Fumarate ratio for assessing SDH dysfunction in different tumor types.
Kim, Edward; Wright, Michael Jp; Sioson, Loretta; Novos, Talia; Gill, Anthony J; Benn, Diana E; White, Christopher; Dwight, Trisha; Clifton-Bligh, Roderick J.
Afiliación
  • Kim E; Cancer Genetics, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, Australia; University of Sydney, Sydney, Australia.
  • Wright MJ; Clinical Chemistry, South Eastern Area Laboratory Services Pathology, Prince of Wales Private Hospital, Sydney, Australia.
  • Sioson L; Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, Australia.
  • Novos T; Clinical Chemistry, South Eastern Area Laboratory Services Pathology, Prince of Wales Private Hospital, Sydney, Australia.
  • Gill AJ; Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, Australia; University of Sydney, Sydney, Australia.
  • Benn DE; Cancer Genetics, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, Australia; University of Sydney, Sydney, Australia.
  • White C; Clinical Chemistry, South Eastern Area Laboratory Services Pathology, Prince of Wales Private Hospital, Sydney, Australia; Department of Endocrinology and Diabetes, Prince of Wales Hospital, Sydney, Australia.
  • Dwight T; Cancer Genetics, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, Australia; University of Sydney, Sydney, Australia.
  • Clifton-Bligh RJ; Cancer Genetics, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, Australia; University of Sydney, Sydney, Australia.
Mol Genet Metab Rep ; 10: 45-49, 2017 Mar.
Article en En | MEDLINE | ID: mdl-28070496
OBJECTIVE: Mutations of genes encoding the four subunits of succinate dehydrogenase (SDH) have been associated with pheochromocytoma and paraganglioma (PPGLs), gastrointestinal stromal tumors (GISTs) and renal cell carcinomas (RCCs). These tumors have not been characterized in a way that reflects severity of SDH dysfunction. Mass spectrometric analysis now allows measurement of metabolites extracted from formalin fixed paraffin embedded (FFPE) specimens. We assess whether SDH deficiency in various tumor types characterized by loss of SDHB protein expression correlates with SDH dysfunction as assessed by the ratio of succinate:fumarate in FFPE specimens. PATIENTS AND METHODS: Sections of FFPE tumor specimens from 18 PPGL, 10 GIST and 11 RCC patients with known SDHx mutation status for SDH deficiency were collected for mass spectrometric analysis of succinate and fumarate. RESULTS: FFPE samples showed higher succinate:fumarate ratios in SDH-deficient PPGLs compared to SDH-sufficient PPGLs. Similarly, a higher succinate:fumarate ratio was able to distinguish SDH-deficient GISTs and RCCs from their SDH-sufficient counterparts with great selectivity. Interestingly, the cut-off value of the succinate:fumarate ratio was two-folds greater in RCCs than GISTs. CONCLUSION: Analyzing biochemical imbalances preserved in FFPE specimens with mass spectrometry expands the method and sample type repertoire available for characterisation of multiple neoplasias associated with SDH deficiency.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Mol Genet Metab Rep Año: 2017 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Mol Genet Metab Rep Año: 2017 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos