Pheochromocytoma and paraganglioma: implications of germline mutation investigation for treatment, screening, and surveillance

ABSTRACT Objective Paraganglioma (PGL) and pheochromocytoma (PCC) are rare neuroendocrine tumors that were considered to be predominantly sporadic. However, with the identification of novel susceptibility genes over the last decade, it is currently estimated that up to 40% of cases can occur in the context of a hereditary syndrome. We aimed to characterize PGL/PCC families to exemplify the different scenarios in which hereditary syndromes can be suspected and to emphasize the importance for patients and their families of making an opportune genetic diagnosis. Materials and methods Retrospective analysis of patients diagnosed with PGL/PCC. Germline mutations were studied using next-generation sequencing panels including SDHA, SDHB, SDHC and SDHD. Clinical data were collected from clinical records, and all patients received genetic counseling. Results We describe 4 families with PGL/PCC and germline mutations in SDH complex genes. 2 families have SDHB mutations and 2 SDHD mutations. The clinical presentation of the patients and their families was heterogeneous, with some being atypical according to the literature. Conclusions PGL/PCC are more commonly associated with a germline mutation than any other cancer type, therefore, all individuals with these types of tumors should undergo genetic risk evaluation. NGS multigene panel testing is a cost-effective approach given the overlapping phenotypes. Individuals with germline mutations associated with PGL/PCC should undergo lifelong clinical, biochemical and imaging surveillance and their families should undergo genetic counseling. For all these reasons, it is critical that all medical staff can suspect and diagnose these inherited cancer predisposition syndromes.

Effect of succinate dehydrogenase complex subunit A gene knockdown on cell proliferation,cell cycle and apoptosis of mouse hepatic cell line BNL CL.2 cells / 中国药理学与毒理学杂志

OBJECTIVE To investigate the effect of succinate dehydrogenase complex subunit A (sdha)gene on cell proliferation,cell cycle and apoptosis of mouse hepatic cell line BNL CL.2 cells. METHODS The BNL CL.2 cells were transfected by two kinds of sdha-shRNA lentivirus to knockdown sdha gene. The infection efficiency of BNL CL.2 cells infected with lentiviral vectors was analyzed by flow cytometry. The expression of sdha gene and SDHA protein was detected by real-time PCR and Western blotting,respectively. The effect of sdha gene on cell proliferation of BNL CL.2 cells was examined by growth curve,while cell cycle and apoptosis were analyzed by flow cytometry. RESULTS The infection efficiency of BNL CL.2 cells in sh-control group and in sdha-shRNA group was above 80%. Compared with sh-control group,the expression of sdha gene in BNL CL.2 cells infected with sdha-shRNA lentivirus was decreased by about 20 times(P<0.01),the expression of SDHA protein was decreased by about 10 times(P<0.01),and the growth rate was about 70%that of sh-control group(P<0.05). The cells were arrested in S phase,and the percentage of cells in S phase was 0.74 times that of sh-control group(P<0.01). The percentage of cells in G0/GI phase was 1.17 times that of sh-control group(P<0.01). The percentage of cells in G2/M was 1.37 times that of sh-control group(P<0.01). But there was no obvious difference in the apoptosis rate. CONCLUSION The reduced expression of SDHA protein can inhibit the proliferation of mouse hepatic cells,and the inhibitory mechanism may be cell cycle arrest. There is possibly no relationship between inhibition and cell apoptosis.

Study on the mutations of SDHD gene in sporadic pheochromocytoma in Chongqing / 重庆医科大学学报

Objective:To study the association between mutations in the first and second exons of(Succtnate dehydrogenaes complex,subunit D(SDHD)gene and sporadic pheochromocytoma in Chongqing Methods:Polymerase chain reaction combining with single strand conformation polymorphism(PCR-SSCP)was selected to analysis the mutations in the first and second exons of SDHD gene in 32 cases of sporadic pheochromocytoma who were diagnosed by pathology(including 21 cases of pheochromocytoma and 11 cases of extra-adrenal paraganglioma)and 80 cases of the healthy controls.Results:No mutation was found in the first and second exons of SDHD gene in the 32 patients.Conclusion:In our study,we had not found any mutation in the first and second exons of SDHD gene in sporadic pheochromo-cytoma in Chongqing.