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Cancer Res:全基因组测序技术深入剖析前列腺癌

来源:生物谷 2013-05-27 23:55

2013年5月26日 讯 /生物谷BIOON/ --近日,刊登在国际杂志Cancer Research上的一篇研究报告中,来自梅奥诊所的研究者使用新一代的基因组分析技术揭示了,某些恶性的前列腺癌肿瘤具有相似的遗传起源过程,这或许可以帮助研究者来对癌症恶化进行预测。

研究者John Cheville博士表示,这项研究首次揭示了,使用新一代的测序技术对相同肿瘤的DNA改变进行检测将使得研究者在病理学上更加快速地了解肿瘤的基因组改变情况。

目前评估前列腺癌活组织样品的标准方法就是通过一种称为格里森分级系统的方法来进行的,病理学家在显微镜下对肿瘤样品进行检测,将会基于细胞的模式给出一个格里森分数,然而许多前列腺癌包含不仅仅一种模式,最常见的两种模式结合起来可以给出一个格里森分数,分值越高肿瘤越恶性。

研究者Cheville说道,当每种模式都有自己的断点时,他们会公用同一个,这样就会出现共同的起源了。恶性前列腺癌相关的DNA改变通常是在低格里森模式下被鉴别出的,这也就揭示了,在基因组被识别之前,其改变就已经发生了。

通过理解肿瘤间的谱系关系,研究者就可以更好地对癌症进行预测,从而合理有效地控制病人的治疗。为了确定每个肿瘤样品的格里森模式间的关系,研究小组使用激光捕获显微解剖法,对14个肿瘤进行了检测,发现了在所有的肿瘤中出现了超过3000个独特的染色体改变;相关研究由Waterman Biomarker Discovery等进行资助。(生物谷Bioon.com)

Lineage Relationship of Gleason Patterns in Gleason Score 7 Prostate Cancer

Irina V. Kovtun1, John C. Cheville2, Stephen J. Murphy3, Sarah H. Johnson3, Shabnam Zarei3, Farhad Kosari3, William R. Sukov2, R. Jeffrey Karnes4, and George Vasmatzis3

Gleason score 7 (GS7) prostate cancer [tumors with both Gleason patterns 3 (GP3) and 4 (GP4)] portends a significantly more aggressive tumor than Gleason score 6 (GS6). It is, therefore, critical to understand the molecular relationship of adjacent GP3 and GP4 tumor cell populations and relate molecular abnormalities to disease progression. To decipher molecular relatedness, we used laser capture microdissection (LCM) and whole-genome amplification (WGA) to separately collect and amplify DNA from adjacent GP3 and GP4 cell populations from 14 cases of GS7 prostate cancer. We then carried out massively parallel mate-pair next generation sequencing (NGS) to examine the landscape of large chromosomal alterations. We identified four to 115 DNA breakpoints in GP3 and 17 to 480 in GP4. Our findings indicate that while GP3 and GP4 from the same tumor each possess unique breakpoints, they also share identical ones, indicating a common origin. Approximately 300 chromosomal breakpoints were localized to the regions affected in at least two tumors, whereas more than 3,000 were unique within the set of 14 tumors. TMPRSS2–ERG was the most recurrent rearrangement present in eight cases, in both GP3 and GP4. PTEN rearrangements were found in five of eight TMPRSS2–ERG fusion–positive cases in both GP3 and GP4. Hierarchical clustering analysis revealed that GP3 has greater breakpoint similarity to its partner GP4 compared with GP3 from different patients. We show evidence that LCM, WGA, and NGS of adjacent tumor regions provide an important tool in deciphering lineage relationships and discovering chromosomal alterations associated with tumor progression. Cancer Res; 73(11); 1–10. ©2013 AACR.

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