SDHD体细胞和神秘的胚系突变,线粒体复杂II基因,在分家嗜铬细胞瘤。
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Gimm O, Armanios一直M, Dziema H,诺伊曼惠普,Eng C
SDHD体细胞和神秘的胚系突变,线粒体复杂II基因,在分家嗜铬细胞瘤。
癌症研究》2000年12月15日,60 (24):6822 - 5。
- PubMed ID
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11156372 (在PubMed]
- 文摘
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嗜铬细胞瘤最零星的,但虽然是世袭的约10%。尽管大多数继承了嗜铬细胞瘤的病因是众所周知的,更常见的病因是鲜为人知的零星的肿瘤。SDHD的生殖细胞突变,最近一个线粒体复杂II基因,遗传副神经节瘤患者被发现。我们试图确定SDHD嗜铬细胞瘤在零星的发展过程中发挥作用,进行了突变和删除SDHD分析。在18个样本,我们发现4杂合的序列变异(3细胞1体)。一个胚系突变SDHD IVS1 + 2 t > G(缺席78控制等位基因)预计将导致异常剪接。重新调查,这个病人被发现有颈动脉体的肿瘤,这可能是一个副神经节瘤。后,另一个病人恶性嗜铬细胞瘤extra-adrenal被发现带有c。34 g > (g12)。然而,这种序列变异还发现78年1等位基因控制。第三,细胞无义突变R38X被发现在一个病人extra-adrenal嗜铬细胞瘤。 The only somatic heterozygous mutation, c.242C>T (P81L), has been found in the germ line of two families with hereditary paraganglioma and is conserved among four eukaryotic multicellular organisms. Hence, this mutation is most likely of functional significance too. Overall, loss of heterozygosity in at least one of the two markers flanking SDHD was found in 13 tumors (72%). All of the tumors that already harbored intragenic SDHD mutations, whether germ-line or somatic, also had loss of heterozygosity. Our results indicate that SDHD plays a role in the pathogenesis of pheochromocytoma. Given the minimum estimated germline SDHD mutation frequency of 11% (maximum estimate up to 17%) in this set of apparently sporadic pheochromocytoma cases and if these data can be replicated in other populations, our observations might suggest that all such patients be considered for SDHD mutation analysis.