新浪登录
腾讯登录Nature：胰腺癌全基因组分析揭示疾病的新型路径
| 导读 | 近日，刊登在国际杂志<em>Nature</em>上的一篇研究报告中，来自贝勒医学院的研究者表示，在对胰腺肿瘤的一项最新的基因组分析中，研究者发现了参与这个疾病发病的两条途径，这就为开发新型以及早期的疾病检测手段提供了帮助。
<!--more-->
研究者Fisher表示，如今我们知道了参与胰腺癌发病的每一个基因，这对于我们深入解析该疾病的发病机理带... |
近日，刊登在国际杂志<em>Nature</em>上的一篇研究报告中，来自贝勒医学院的研究者表示，在对胰腺肿瘤的一项最新的基因组分析中，研究者发现了参与这个疾病发病的两条途径，这就为开发新型以及早期的疾病检测手段提供了帮助。
<!--more-->
研究者Fisher表示，如今我们知道了参与胰腺癌发病的每一个基因，这对于我们深入解析该疾病的发病机理带来了巨大帮助。贝勒医学院人类基因组测序中心（BCM）是世界上三大测序中心之一，研究者对142位胰腺癌患者的组织进行了相关的基因组测序分析。与此同时，BCM同澳大利亚胰腺测序中心、安大略胰腺癌测序中心的研究者完成了99项胰腺肿肿瘤的详细测序，鉴别出了1982个发生在蛋白上的突变以及1628项明显的染色体结构复制数目的突变。
研究者表示，这是我们之间并没有发现的和胰腺癌相关的一些基因，我们希望去深入研究这些基因以获得更多的关于胰腺癌发病的一些信息。胰腺癌是第四大引发人类癌症死亡的元凶，患者5年存活率低于5%。
这项最新的研究也是报道关于该疾病的原发性肿瘤的一些研究发现，此前仅仅有移植入小鼠体内的细胞系或者肿瘤可以使用，因为肿瘤非常小，因此研究者需要使用新型的技术来敏感性地识别肿瘤相关的遗传突变，这对于理解疾病的进展非常有帮助。
研究者表示，这项大型的多中心的研究中，使用了多组癌症患者进行研究，对于引导研究者开发新型胰腺癌疗法非常重要。
编译自：<a title="" href="http://www.sciencedaily.com/releases/2012/10/121024133353.htm" target="_blank">Genome Analysis of Pancreas Tumors Reveals New Pathway</a>
<div id="ztload">
<div> </div>
<div>
<div>
<img src="http://www.bioon.com/biology/UploadFiles/201210/2012102523151342.jpg" alt="" width="113" height="149" border="0" />
<a title="" href="http://dx.doi.org/doi:10.1038/nature11547" target="_blank">doi:10.1038/nature11547</a>
PMC:
PMID:
</div>
<div>
<br/><strong>Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes</strong><br/>
Andrew V. Biankin Nicola Waddell Karin S. Kassahn Marie-Claude Gingras Lakshmi B. Muthuswamy Amber L. Johns David K. Miller Peter J. Wilson Ann-Marie Patch Jianmin Wu David K. Chang Mark J. Cowley Brooke B. Gardiner Sarah Song Ivon Harliwong Senel Idrisoglu Craig Nourse Ehsan Nourbakhsh Suzanne Manning Shivangi Wani Milena Gongora Marina Pajic Christopher J. Scarlett Anthony J. Gill Andreia V. Pinho Ilse Rooman Matthew Anderson Oliver Holmes Conrad Leonard Darrin Taylor Scott Wood Christina Xu Katia Nones J. Lynn Fink Angelika Christ Tim Bruxner Nicole Cloonan Gabriel Kolle Felicity Newell Mark Pinese R. Scott Mead Jeremy L. Humphris Warren Kaplan Marc D. Jones Emily K. Colvin Adnan M. Nagrial Emily S. Humphrey Angela Chou Venessa T. Chin Lorraine A. Chantrill Amanda Mawson Jaswinder S. Samra James G. Kench Jessica A. Lovell Roger J. Daly Neil D. Merrett Christopher Toon Krishna Epari Nam Q. Nguyen Andrew Barbour Nikolajs Zeps Australian Pancreatic Cancer Genome Initiative Nipun Kakkar Fengmei Zhao Yuan Qing Wu Min Wang Donna M. Muzny William E. Fisher F. Charles Brunicardi Sally E. Hodges Jeffrey G. Reid Jennifer Drummond Kyle Chang Yi Han Lora R. Lewis Huyen Dinh Christian J. Buhay Timothy Beck Lee Timms Michelle Sam Kimberly Begley Andrew Brown Deepa Pai Ami Panchal Nicholas Buchner Richard De Borja Robert E. Denroche Christina K. Yung Stefano Serra Nicole Onetto Debabrata Mukhopadhyay Ming-Sound Tsao Patricia A. Shaw Gloria M. Petersen Steven Gallinger Ralph H. Hruban Anirban Maitra Christine A. Iacobuzio-Donahue Richard D. Schulick Christopher L. Wolfgang Richard A. Morgan Rita T. Lawlor Paola Capelli Vincenzo Corbo Maria Scardoni Giampaolo Tortora Margaret A. Tempero Karen M. Mann Nancy A. Jenkins Pedro A. Perez-Mancera David J. Adams David A. Largaespada Lodewyk F. A. Wessels Alistair G. Rust Lincoln D. Stein David A. Tuveson Neal G. Copeland Elizabeth A. Musgrove Aldo Scarpa James R. Eshleman Thomas J. Hudson Robert L. Sutherland David A. Wheeler John V. Pearson John D. McPherson Richard A. Gibbs Sean M. Grimmond
Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis.
<br/>来源：生物谷
</div>
</div>
</div>
<!--more-->
研究者Fisher表示，如今我们知道了参与胰腺癌发病的每一个基因，这对于我们深入解析该疾病的发病机理带来了巨大帮助。贝勒医学院人类基因组测序中心（BCM）是世界上三大测序中心之一，研究者对142位胰腺癌患者的组织进行了相关的基因组测序分析。与此同时，BCM同澳大利亚胰腺测序中心、安大略胰腺癌测序中心的研究者完成了99项胰腺肿肿瘤的详细测序，鉴别出了1982个发生在蛋白上的突变以及1628项明显的染色体结构复制数目的突变。
研究者表示，这是我们之间并没有发现的和胰腺癌相关的一些基因，我们希望去深入研究这些基因以获得更多的关于胰腺癌发病的一些信息。胰腺癌是第四大引发人类癌症死亡的元凶，患者5年存活率低于5%。
这项最新的研究也是报道关于该疾病的原发性肿瘤的一些研究发现，此前仅仅有移植入小鼠体内的细胞系或者肿瘤可以使用，因为肿瘤非常小，因此研究者需要使用新型的技术来敏感性地识别肿瘤相关的遗传突变，这对于理解疾病的进展非常有帮助。
研究者表示，这项大型的多中心的研究中，使用了多组癌症患者进行研究，对于引导研究者开发新型胰腺癌疗法非常重要。
编译自：<a title="" href="http://www.sciencedaily.com/releases/2012/10/121024133353.htm" target="_blank">Genome Analysis of Pancreas Tumors Reveals New Pathway</a>
<div id="ztload">
<div> </div>
<div>
<div>
<img src="http://www.bioon.com/biology/UploadFiles/201210/2012102523151342.jpg" alt="" width="113" height="149" border="0" />
<a title="" href="http://dx.doi.org/doi:10.1038/nature11547" target="_blank">doi:10.1038/nature11547</a>
PMC:
PMID:
</div>
<div>
<br/><strong>Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes</strong><br/>
Andrew V. Biankin Nicola Waddell Karin S. Kassahn Marie-Claude Gingras Lakshmi B. Muthuswamy Amber L. Johns David K. Miller Peter J. Wilson Ann-Marie Patch Jianmin Wu David K. Chang Mark J. Cowley Brooke B. Gardiner Sarah Song Ivon Harliwong Senel Idrisoglu Craig Nourse Ehsan Nourbakhsh Suzanne Manning Shivangi Wani Milena Gongora Marina Pajic Christopher J. Scarlett Anthony J. Gill Andreia V. Pinho Ilse Rooman Matthew Anderson Oliver Holmes Conrad Leonard Darrin Taylor Scott Wood Christina Xu Katia Nones J. Lynn Fink Angelika Christ Tim Bruxner Nicole Cloonan Gabriel Kolle Felicity Newell Mark Pinese R. Scott Mead Jeremy L. Humphris Warren Kaplan Marc D. Jones Emily K. Colvin Adnan M. Nagrial Emily S. Humphrey Angela Chou Venessa T. Chin Lorraine A. Chantrill Amanda Mawson Jaswinder S. Samra James G. Kench Jessica A. Lovell Roger J. Daly Neil D. Merrett Christopher Toon Krishna Epari Nam Q. Nguyen Andrew Barbour Nikolajs Zeps Australian Pancreatic Cancer Genome Initiative Nipun Kakkar Fengmei Zhao Yuan Qing Wu Min Wang Donna M. Muzny William E. Fisher F. Charles Brunicardi Sally E. Hodges Jeffrey G. Reid Jennifer Drummond Kyle Chang Yi Han Lora R. Lewis Huyen Dinh Christian J. Buhay Timothy Beck Lee Timms Michelle Sam Kimberly Begley Andrew Brown Deepa Pai Ami Panchal Nicholas Buchner Richard De Borja Robert E. Denroche Christina K. Yung Stefano Serra Nicole Onetto Debabrata Mukhopadhyay Ming-Sound Tsao Patricia A. Shaw Gloria M. Petersen Steven Gallinger Ralph H. Hruban Anirban Maitra Christine A. Iacobuzio-Donahue Richard D. Schulick Christopher L. Wolfgang Richard A. Morgan Rita T. Lawlor Paola Capelli Vincenzo Corbo Maria Scardoni Giampaolo Tortora Margaret A. Tempero Karen M. Mann Nancy A. Jenkins Pedro A. Perez-Mancera David J. Adams David A. Largaespada Lodewyk F. A. Wessels Alistair G. Rust Lincoln D. Stein David A. Tuveson Neal G. Copeland Elizabeth A. Musgrove Aldo Scarpa James R. Eshleman Thomas J. Hudson Robert L. Sutherland David A. Wheeler John V. Pearson John D. McPherson Richard A. Gibbs Sean M. Grimmond
Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis.
<br/>来源：生物谷
</div>
</div>
</div>
还没有人评论，赶快抢个沙发