Utility of the succinate: Fumarate ratio for assessing SDH dysfunction in different tumor types.
Utility of the succinate: Fumarate ratio for assessing SDH dysfunction in different tumor types.
复制标题
DOI：
10.1016/j.ymgmr.2016.12.006
复制
发表时间：
2017-03
影响因子：
1.9
通讯作者：
Clifton-Bligh, Roderick J.
中科院分区：
文献类型：
--
作者：
Kim, Edward;Wright, Michael J. P.;Sioson, Loretta;Novos, Talia;Gill, Anthony J.;Benn, Diana E.;White, Christopher;Dwight, Trisha;Clifton-Bligh, Roderick J.
关键词：
编码琥珀酸脱氢酶（SDH）四个亚基的基因突变与嗜铬细胞瘤和副神经节瘤（PPGL）、胃肠道间质瘤（GIST）和肾细胞癌（RCC）相关。这些肿瘤的特征不能反映SDH功能障碍的严重程度。质谱分析现在允许测量从福尔马林固定石蜡包埋（FFPE）标本中提取的代谢物。我们通过FFPE标本中琥珀酸：富马酸的比例评估了以SDHB蛋白表达缺失为特征的各种肿瘤类型中的SDH缺陷是否与SDH功能障碍相关。收集了来自18名PPGL、10名GIST和11名RCC患者的FFPE肿瘤标本切片，这些患者具有已知的SDH缺陷的SDHx突变状态，用于琥珀酸盐和富马酸盐的质谱分析。FFPE样品显示，与SDH充足的PPGL相比，SDH缺乏的PPGL中琥珀酸盐：富马酸盐比率更高。类似地，较高的琥珀酸盐：富马酸盐比率能够以很大的选择性将缺乏SDH的GIST和RCC与其充足SDH的对应物区分开。有趣的是，琥珀酸盐：富马酸盐比例的截止值在RCC中是GIST的两倍。用质谱分析保存在FFPE标本中的生化失衡扩展了可用于表征与SDH缺乏相关的多种肿瘤的方法和样本类型库。
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. 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. 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. 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.
登录
查看更多内容
影响因子：
3.7
作者：
Huang SK;Darfler MM;Nicholl MB;You J;Bemis KG;Tegeler TJ;Wang M;Wery JP;Chong KK;Nguyen L;Scolyer RA;Hoon DS
通讯作者：
Hoon DS
影响因子：
5.8
作者：
Richter, Susan;Peitzsch, Mirko;Eisenhofer, Graeme
通讯作者：
Eisenhofer, Graeme
影响因子：
3.9
作者：
Vicha A;Taieb D;Pacak K
通讯作者：
Pacak K
影响因子：
5
作者：
Crockett, DK;Lin, ZS;Elenitoba-Johnson, KSJ
通讯作者：
Elenitoba-Johnson, KSJ
影响因子：
4.8
作者：
Lendvai, Nikoletta;Pawlosky, Robert;Pacak, Karel
通讯作者：
Pacak, Karel