Gastrointestinal stromal tumour in succinate dehydrogenase subunit B mutation‐associated familial phaeochromocytoma/paraganglioma

Bolland, Mark J; Benn, Diana E.; Croxson, Michael; McCall, John L.; Shaw, James H.; Baillie, Tina; Robinson, Bruce G.

doi:10.1111/j.1445-2197.2006.03855.x

Cited by 16 publications

(9 citation statements)

References 5 publications

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“…Germline mutations result in decreased life span, mitochondrial encephalopathy, and malignancies of chromaffin cells. Germline mutations in SDH have been described in familial paragangliomas and pheochromocytomas [111, 112]. Carney–Stratakis syndrome is a dyad consisting of GIST and paragangliomas inherited in an autosomal dominant pattern with incomplete penetrance.…”

Section: Other Non-tki Based Therapiesmentioning

confidence: 99%

Molecular basis for primary and secondary tyrosine kinase inhibitor resistance in gastrointestinal stromal tumor

Gounder

Maki

2010

Cancer Chemother Pharmacol

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Small molecule kinase inhibitors have irrevocably altered cancer treatment. March 2010 marks the 10th anniversary of using imatinib in gastrointestinal stromal tumors (GIST), a cardinal example of the utility of such targeted therapy in a solid tumor. Before imatinib, metastatic GIST was frustrating to treat due to its resistance to standard cytotoxic chemotherapy. Median survival for patients with metastatic GIST improved from 19 to 60 months with imatinib. In treating patients with GIST, two patterns of tyrosine kinase inhibitor resistance have been observed. In the first, ~9–14% of patients have progression within 3 months of starting imatinib. These patients are classified as having primary or early resistance. Median progression-free survival (PFS) on imatinib is approximately 24 months; patients with later progression are classified as having secondary or acquired resistance. Primary studies and a meta-analysis of studies of imatinib in GIST patients have identified prognostic features that contribute to treatment failure. One of the strongest predictors for success of therapy is KIT or PDGFRA mutational status. Patients with KIT exon 11 mutant GIST have better response rates, PFS, and overall survival compared to other mutations. A great deal has been learned in the last decade about sensitivity and resistance of GIST to imatinib; however, many unanswered questions remain about secondary resistance mechanisms and clinical management in the third- and fourth-line setting. This review will discuss the role of dose effects, and early and late resistance to imatinib and their clinical implications. Patients intolerant to imatinib (5%) and those who progress on imatinib are treated with sunitinib. The mechanism of resistance to sunitinib is unknown at this time but is also appears related to growth of clones with secondary mutations in KIT. Third- and fourth-line treatments of GIST and with future treatment strategies are also discussed.

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Section: Other Non-tki Based Therapiesmentioning

confidence: 99%

Molecular basis for primary and secondary tyrosine kinase inhibitor resistance in gastrointestinal stromal tumor

Gounder

Maki

2010

Cancer Chemother Pharmacol

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“…It has a much higher risk of malignant behavior that may be greater than 50% [1,5,13,14]. There is a also a suggestion of an increased risk of renal cell carcinoma and gastrointestinal stromal tumor [4,11,[15][16][17]. SDH mutations in tumors are virtually always associated with germline mutations, and we are only aware of 2 reports of somatic mutation (1 SDHB and 1 SDHD) in the absence of germline mutation [14,18,19].…”

Section: Introductionmentioning

confidence: 98%

Immunohistochemistry for SDHB triages genetic testing of SDHB, SDHC, and SDHD in paraganglioma-pheochromocytoma syndromes

et al. 2010

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“…Germline mutations of the SDHB, SDHC and SDHD had been previously reported in inherited PGL and pheochromocytoma (PCC) [26][27][28][29][30], but not in familiar GISTs, until they were described in patients with the Carney-Stratakis dyad [25,31].…”

Section: Introductionmentioning

confidence: 98%

A novel germline SDHB mutation in a gastrointestinal stromal tumor patient without bona fide features of the Carney–Stratakis dyad

et al. 2011

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Gastrointestinal stromal tumors (GISTs) are the most common mesenchyme neoplasms of the gastrointestinal tract. Gain-of-function somatic mutations of the KIT or PDGFRA genes represent the most prevalent molecular alterations in GISTs. In Carney-Stratakis dyad, patients portray germline mutations of the succinate dehydrogenase subunits B (SDHB), C (SDHC) and D (SDHD) and develop multifocal GISTs and multicentric paragangliomas (PGLs). We herein report a novel germline SDHB mutation (c.T282A--Ile44Asn) occurring in a 26 years-old patient diagnosed with a spindle cell intermediate risk GIST that did not present KIT/PDGFRA/BRAF gene mutations. Further analyses revealed loss of the wild-type SDHB allele and complete loss of SDHB expression in the tumor tissue. After genetic screening of other family members, we detected in the patient's mother a SDHB mutation without any clinical/laboratorial evidence of GIST or PGL. Altogether, our findings (germline SDHB mutation with absence of PGL in the index case and of GIST and/or PGL in his mother) raise the possibility that this familiar setting corresponds to an incomplete phenotype of the Carney-Stratakis dyad.

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Gastrointestinal stromal tumour in succinate dehydrogenase subunit B mutation‐associated familial phaeochromocytoma/paraganglioma

Cited by 16 publications

References 5 publications

Molecular basis for primary and secondary tyrosine kinase inhibitor resistance in gastrointestinal stromal tumor

Molecular basis for primary and secondary tyrosine kinase inhibitor resistance in gastrointestinal stromal tumor

Immunohistochemistry for SDHB triages genetic testing of SDHB, SDHC, and SDHD in paraganglioma-pheochromocytoma syndromes

A novel germline SDHB mutation in a gastrointestinal stromal tumor patient without bona fide features of the Carney–Stratakis dyad

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