GNAS1 mutations occur more commonly than previously thought in intramuscular myxoma
GNAS1 mutations occur more commonly than previously thought in intramuscular myxoma
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DOI：
10.1038/modpathol.2009.32
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发表时间：
2009-05-01
期刊：
影响因子：
7.5
通讯作者：
Flanagan, Adrienne M.
中科院分区：
文献类型：
--
作者：
Delaney, David;Diss, Tim C.;Flanagan, Adrienne M.
突变检测在诊断病理学中起重要作用，不仅在提供组织诊断中，而且在预测对抗肿瘤发生剂的反应中。然而，突变检测策略经常受到野生型序列对突变等位基因的掩蔽的阻碍。据报道，在较低变性温度下的共扩增PCR（COLD-PCR）通过使用PCR循环增加野生型背景中罕见变体序列的比例，在所述PCR循环中，变性温度降低以有利于具有较低解链温度的产物形成和由次要变体产生的异源双链体。肌内粘液瘤是一种罕见的良性软组织肿瘤，偶尔发生，很少与纤维结构不良（马扎布劳综合征）。纤维性发育不良是由激活GNAS 1突变引起的，在少量肌内粘液瘤中也发现了相同的突变。该研究的目的主要是确定COLD-PCR是否比传统PCR更敏感;这是通过使用这两种方法检测肌内粘液瘤中的GNAS 1突变来实现的。28例肌内粘液瘤中有8例（29%）使用常规PCR然后突变特异性限制性内切酶消化（PCR-MSRED）检测到突变，而28例中有17例（61%）使用COLD-PCR/MSRED检测到突变。在两个病例中检测到突变，其中低级别粘液纤维肉瘤的诊断优于肌内粘液瘤。在另外9例低度恶性和19例高度恶性粘液纤维肉瘤以及另外40例对照样本中未检测到突变。这项研究显示了COLD-PCR与传统PCR相比在突变检测方面的能力，并表明GNAS 1突变检测在区分肌内粘液瘤和低度粘液纤维肉瘤时提高了诊断准确性。现代病理学（2009）22，718-724; doi：10.1038/modpathol.2009.32;在线发表2009年3月13日
Mutation detection plays an important role in diagnostic pathology, not only in providing a tissue diagnosis, but also in predicting response to antitumourigenic agents. However, mutation detection strategies are often hampered by masking of mutant alleles by wild-type sequences. Coamplification at lower denaturation temperature PCR (COLD-PCR) reportedly increases the proportion of rare variant sequences in a wild-type background by using PCR cycles in which the denaturation temperature is reduced to favour product formation with lower melt temperatures and heteroduplexes arising from minor variants. Intramuscular myxoma is a rare benign soft tissue neoplasm that occurs sporadically and less commonly in association with fibrous dysplasia (Mazabraud's syndrome). Fibrous dysplasia results from activating GNAS1 mutations, and the same mutations have been identified in small numbers of intramuscular myxoma. The aim of the study was primarily to establish whether COLD-PCR is more sensitive than conventional PCR; this was achieved by testing for GNAS1 mutations in intramuscular myxomas using the two methodologies. Mutations were detected in 8 of 28 (29%) cases of intramuscular myxomas using conventional PCR followed by mutation-specific restriction enzyme digestion (PCR-MSRED) whereas 17 of 28 (61%) mutations were detected using COLD-PCR/MSRED. Mutations were detected in two cases where a diagnosis of low-grade myxofibrosarcoma had been favoured over intramuscular myxoma. No mutations were detected in an additional 9 low-grade and 19 high-grade myxofibrosarcomas, and another 40 control samples. This study shows the power of COLD-PCR compared with conventional PCR in mutation detection, and shows that GNAS1 mutation detection increases diagnostic accuracy when distinguishing between intramuscular myxoma and low-grade myxofibrosarcoma. Modern Pathology (2009) 22, 718-724; doi: 10.1038/modpathol.2009.32; published online 13 March 2009