Clinical and molecular genetics of patients with the Carney–Stratakis syndrome and germline mutations of the genes coding for the succinate dehydrogenase subunits SDHB, SDHC, and SDHD

被引：0
作者：
Barbara Pasini
Sarah R McWhinney
Thalia Bei
Ludmila Matyakhina
Sotirios Stergiopoulos
Michael Muchow
Sosipatros A Boikos
Barbara Ferrando
Karel Pacak
Guillaume Assie
Eric Baudin
Agnes Chompret
Jay W Ellison
Jean-Jacques Briere
Pierre Rustin
Anne-Paule Gimenez-Roqueplo
Charis Eng
J Aidan Carney
Constantine A Stratakis
机构：
[1] Biology and Biochemistry,Department of Genetics
[2] University of Torino,Department of Molecular Genetics
[3] The Ohio State University,Département d'Endocrinologie
[4] Section on Endocrinology and Genetics,Department of Medical Genetics
[5] Pediatric Endocrinology Training Program,Department of Genetics
[6] Developmental Endocrinology Branch,Department of Laboratory Medicine and Pathology
[7] National Institutes of Health,undefined
[8] Reproductive Biology and Medicine Branch,undefined
[9] National Institute of Child Health and Human Development,undefined
[10] National Institutes of Health,undefined
[11] INSERM U567,undefined
[12] Institut Cochin,undefined
[13] Cancerologie Endocrinienne,undefined
[14] Institut Gustave Roussy,undefined
[15] Oncogenetique,undefined
[16] Institut Gustave Roussy,undefined
[17] Mayo Clinic,undefined
[18] INSERM,undefined
[19] U676,undefined
[20] Faculté de Médecine Denis Diderot,undefined
[21] Université Paris 7,undefined
[22] IFR02,undefined
[23] Assistance Publique-Hopitaux de Paris,undefined
[24] Hopital Européen Georges Pompidou,undefined
[25] Faculté de Médecine,undefined
[26] Université Paris-Descartes,undefined
[27] INSERM,undefined
[28] U772,undefined
[29] College de France,undefined
[30] Genomic Medicine Institute,undefined
[31] Lerner Research Institute and Taussig Cancer Center,undefined
[32] Cleveland Clinic Foundation,undefined
[33] Mayo Clinic,undefined
来源：
European Journal of Human Genetics | 2008年 / 16卷
关键词：
gastrointestinal stromal tumors; succinate dehydrogenase subunits B, C and D; paraganglioma; tumor suppressor gene;
D O I：
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中图分类号：
学科分类号：
摘要：
Gastrointestinal stromal tumors (GISTs) may be caused by germline mutations of the KIT and platelet-derived growth factor receptor-α (PDGFRA) genes and treated by Imatinib mesylate (STI571) or other protein tyrosine kinase inhibitors. However, not all GISTs harbor these genetic defects and several do not respond to STI571 suggesting that other molecular mechanisms may be implicated in GIST pathogenesis. In a subset of patients with GISTs, the lesions are associated with paragangliomas; the condition is familial and transmitted as an autosomal-dominant trait. We investigated 11 patients with the dyad of ‘paraganglioma and gastric stromal sarcoma’; in eight (from seven unrelated families), the GISTs were caused by germline mutations of the genes encoding subunits B, C, or D (the SDHB, SDHC and SDHD genes, respectively). In this report, we present the molecular effects of these mutations on these genes and the clinical information on the patients. We conclude that succinate dehydrogenase deficiency may be the cause of a subgroup of GISTs and this offers a therapeutic target for GISTs that may not respond to STI571 and its analogs.
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页码：79 / 88
页数：9
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