Loss of heterozygosity of succinate dehydrogenase B mutation by direct sequencing in synchronous paragangliomas

Prasad, Pinki; Kant, Jeffrey A.; Wills, Marcia L.; O'Leary, Mandy F.; Lovvorn, Harold N.; Yang, Elizabeth

doi:10.1016/j.cancergencyto.2009.04.009

Cited by 5 publications

(2 citation statements)

References 11 publications

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“…The functional consequences of this mutation were explored by immunostaining of the protein. Loss of expression of SDHB protein was an argument for the loss of wild-type SDHB allele in the tumor, a mechanism already involved in SDHB-related tumors (12,13).…”

Section: Discussionmentioning

confidence: 99%

A SDHB malignant paraganglioma with dramatic response to temozolomide–capecitabine

Nozières

Walter²,

Joly³

et al. 2012

European Journal of Endocrinology

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Ten percent of paragangliomas are malignant and one-third occurs in a genetic background. We report a case of succinate dehydrogenase subunit B (SDHB)-related malignant paraganglioma with dramatic response to temozolomide and capecitabine regimen (decrease in tumor size of 70% with RECIST criteria). Tumor cells harbored a new mutation in SDHB gene and showed aberrant hypermethylation of O6-methylguanine-DNA-methyltransferase promoter. Our report suggests the importance of molecular predictive factors of response for the selection of chemotherapeutic as well as targeted agents. This observation points to a possible genotype response to treatment relationships, which could help to design tailor-made treatments in the future.

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Section: Discussionmentioning

confidence: 99%

A SDHB malignant paraganglioma with dramatic response to temozolomide–capecitabine

Nozières

Walter²,

Joly³

et al. 2012

European Journal of Endocrinology

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“…The tumors arise via a classic ‘two-hit’ mechanism in which the wild type allele is somehow disabled, either by deletion or by mutation. The loss of the wild-type in the affected cells can be seen on DNA analysis and on histochemistry [ 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

Model systems in SDHx-related pheochromocytoma/paraganglioma

Takács‐Vellai

Farkas

Ősz

et al. 2021

Cancer Metastasis Rev

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Pheochromocytoma (PHEO) and paraganglioma (PGL) (together PPGL) are tumors with poor outcomes that arise from neuroendocrine cells in the adrenal gland, and sympathetic and parasympathetic ganglia outside the adrenal gland, respectively. Many follow germline mutations in genes coding for subunits of succinate dehydrogenase (SDH), a tetrameric enzyme in the tricarboxylic acid (TCA) cycle that both converts succinate to fumarate and participates in electron transport. Germline SDH subunit B (SDHB) mutations have a high metastatic potential. Herein, we review the spectrum of model organisms that have contributed hugely to our understanding of SDH dysfunction. In Saccharomyces cerevisiae (yeast), succinate accumulation inhibits alpha-ketoglutarate-dependent dioxygenase enzymes leading to DNA demethylation. In the worm Caenorhabditis elegans, mutated SDH creates developmental abnormalities, metabolic rewiring, an energy deficit and oxygen hypersensitivity (the latter is also found in Drosophila melanogaster). In the zebrafish Danio rerio, sdhb mutants display a shorter lifespan with defective energy metabolism. Recently, SDHB-deficient pheochromocytoma has been cultivated in xenografts and has generated cell lines, which can be traced back to a heterozygous SDHB-deficient rat. We propose that a combination of such models can be efficiently and effectively used in both pathophysiological studies and drug-screening projects in order to find novel strategies in PPGL treatment.

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Pediatric Paragangliomas: Role of Germline Mutation in Succinate Dehydrogenase

Prasad

Yang

2012

Pediatric Cancer

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Loss of heterozygosity of succinate dehydrogenase B mutation by direct sequencing in synchronous paragangliomas

Cited by 5 publications

References 11 publications

A SDHB malignant paraganglioma with dramatic response to temozolomide–capecitabine

A SDHB malignant paraganglioma with dramatic response to temozolomide–capecitabine

Model systems in SDHx-related pheochromocytoma/paraganglioma

Pediatric Paragangliomas: Role of Germline Mutation in Succinate Dehydrogenase

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