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腾讯登录Nat Gene：揭示和黑色素瘤相关的基因突变
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近日，刊登在国际杂志<em>Nature Genetics</em>上的一篇研究报告中，科学家们发现饿了和黑色素瘤发展相关的新的基因突变。在皮肤癌患者死亡病例中，黑色素瘤占据了绝大多数。促使黑色素瘤的主要原因是过度暴露在太阳紫外线照射下。
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来自耶鲁癌症研究中心的研究者使用DNA序列分析技术分析了147个黑色素瘤患者身体暴露于太阳光下和隔离的身体部位，通过研究，研究者在太阳光暴露部位发现了紫外线诱导的基因突变，但是大部分的突变对疾病的发展并不重要。
研究者Michael表示，我们设计了一个数学模型，用以将来自25，000个突变的相关DNA修饰进行分类，研究者发现在RAC1基因上的突变可以加速正常皮肤色素细胞的生长和移动，这就预示着黑色素瘤的开始。这种突变在黑色素瘤发展早期开始发生，并且可以促进癌症细胞的生长以及机体的全身扩散。
RAC1的突变在大约9%的日光暴露黑色素瘤患者身上发现，由于RAC1突变如此频繁，因此研究者指出，以该基因为靶点可以开发出新的治疗药物。
目前在美国大约每年有76，000个人被诊断患有黑色素瘤，每年会有9000人死于该疾病，因此研究者希望尽快开发出新的治疗手段以应对该疾病。
编译自：<a title="" href="http://medicalxpress.com/news/2012-07-scientists-uncover-gene-variation-linked.html" target="_blank">Scientists uncover gene variation linked to melanoma</a>
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<a title="" href="http://dx.doi.org/doi:10.1038/ng.2359" target="_blank">doi:10.1038/ng.2359</a>
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<br/><strong>Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma</strong><br/>
Michael Krauthammer, Yong Kong, Byung Hak Ha, Perry Evans, Antonella Bacchiocchi, James P McCusker, Elaine Cheng, Matthew J Davis, Gerald Goh, Murim Choi, Stephan Ariyan, Deepak Narayan, Ken Dutton-Regester, Ana Capatana, Edna C Holman, Marcus Bosenberg, Mario Sznol, Harriet M Kluger, Douglas E Brash, David F Stern, Miguel A Materin, Roger S Lo, Shrikant Mane, Shuangge Ma, Kenneth K Kidd et al.
We characterized the mutational landscape of melanoma, the form of skin cancer with the highest mortality rate, by sequencing the exomes of 147 melanomas. Sun-exposed melanomas had markedly more ultraviolet (UV)-like C>T somatic mutations compared to sun-shielded acral, mucosal and uveal melanomas. Among the newly identified cancer genes was PPP6C, encoding a serine/threonine phosphatase, which harbored mutations that clustered in the active site in 12% of sun-exposed melanomas, exclusively in tumors with mutations in BRAF or NRAS. Notably, we identified a recurrent UV-signature, an activating mutation in RAC1 in 9.2% of sun-exposed melanomas. This activating mutation, the third most frequent in our cohort of sun-exposed melanoma after those of BRAF and NRAS, changes Pro29 to serine (RAC1P29S) in the highly conserved switch I domain. Crystal structures, and biochemical and functional studies of RAC1P29S showed that the alteration releases the conformational restraint conferred by the conserved proline, causes an increased binding of the protein to downstream effectors, and promotes melanocyte proliferation and migration. These findings raise the possibility that pharmacological inhibition of downstream effectors of RAC1 signaling could be of therapeutic benefit.
<br/>来源：生物谷
<em>全球分子诊断网（</em><em><a href="http://www.360zhyx.com">www.zhenduan.org</a></em><em>）</em>
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</div>
<p align="center"><img src="http://www.bioon.com/biology/UploadFiles/201207/2012073021260535.jpg" alt="" width="180" height="119" border="0" /></p>
近日，刊登在国际杂志<em>Nature Genetics</em>上的一篇研究报告中，科学家们发现饿了和黑色素瘤发展相关的新的基因突变。在皮肤癌患者死亡病例中，黑色素瘤占据了绝大多数。促使黑色素瘤的主要原因是过度暴露在太阳紫外线照射下。
<!--more-->
来自耶鲁癌症研究中心的研究者使用DNA序列分析技术分析了147个黑色素瘤患者身体暴露于太阳光下和隔离的身体部位，通过研究，研究者在太阳光暴露部位发现了紫外线诱导的基因突变，但是大部分的突变对疾病的发展并不重要。
研究者Michael表示，我们设计了一个数学模型，用以将来自25，000个突变的相关DNA修饰进行分类，研究者发现在RAC1基因上的突变可以加速正常皮肤色素细胞的生长和移动，这就预示着黑色素瘤的开始。这种突变在黑色素瘤发展早期开始发生，并且可以促进癌症细胞的生长以及机体的全身扩散。
RAC1的突变在大约9%的日光暴露黑色素瘤患者身上发现，由于RAC1突变如此频繁，因此研究者指出，以该基因为靶点可以开发出新的治疗药物。
目前在美国大约每年有76，000个人被诊断患有黑色素瘤，每年会有9000人死于该疾病，因此研究者希望尽快开发出新的治疗手段以应对该疾病。
编译自：<a title="" href="http://medicalxpress.com/news/2012-07-scientists-uncover-gene-variation-linked.html" target="_blank">Scientists uncover gene variation linked to melanoma</a>
<div id="ztload">
<div> </div>
<div>
<div>
<img src="http://www.bioon.com/biology/UploadFiles/201207/2012073021273915.jpg" alt="" width="113" height="149" border="0" />
<a title="" href="http://dx.doi.org/doi:10.1038/ng.2359" target="_blank">doi:10.1038/ng.2359</a>
PMC:
PMID:
</div>
<div>
<br/><strong>Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma</strong><br/>
Michael Krauthammer, Yong Kong, Byung Hak Ha, Perry Evans, Antonella Bacchiocchi, James P McCusker, Elaine Cheng, Matthew J Davis, Gerald Goh, Murim Choi, Stephan Ariyan, Deepak Narayan, Ken Dutton-Regester, Ana Capatana, Edna C Holman, Marcus Bosenberg, Mario Sznol, Harriet M Kluger, Douglas E Brash, David F Stern, Miguel A Materin, Roger S Lo, Shrikant Mane, Shuangge Ma, Kenneth K Kidd et al.
We characterized the mutational landscape of melanoma, the form of skin cancer with the highest mortality rate, by sequencing the exomes of 147 melanomas. Sun-exposed melanomas had markedly more ultraviolet (UV)-like C>T somatic mutations compared to sun-shielded acral, mucosal and uveal melanomas. Among the newly identified cancer genes was PPP6C, encoding a serine/threonine phosphatase, which harbored mutations that clustered in the active site in 12% of sun-exposed melanomas, exclusively in tumors with mutations in BRAF or NRAS. Notably, we identified a recurrent UV-signature, an activating mutation in RAC1 in 9.2% of sun-exposed melanomas. This activating mutation, the third most frequent in our cohort of sun-exposed melanoma after those of BRAF and NRAS, changes Pro29 to serine (RAC1P29S) in the highly conserved switch I domain. Crystal structures, and biochemical and functional studies of RAC1P29S showed that the alteration releases the conformational restraint conferred by the conserved proline, causes an increased binding of the protein to downstream effectors, and promotes melanocyte proliferation and migration. These findings raise the possibility that pharmacological inhibition of downstream effectors of RAC1 signaling could be of therapeutic benefit.
<br/>来源：生物谷
<em>全球分子诊断网（</em><em><a href="http://www.360zhyx.com">www.zhenduan.org</a></em><em>）</em>
<em></em>
</div>
</div>
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