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使用阵列比较基因组杂交技术估计正常样本、癌细胞系和实体瘤中DNA拷贝数的计算方法。

Computational method for estimating DNA copy numbers in normal samples, cancer cell lines, and solid tumors using array comparative genomic hybridization.

作者信息

Abkevich Victor, Iliev Diana, Timms Kirsten M, Tran Thanh, Skolnick Mark, Lanchbury Jerry S, Gutin Alexander

机构信息

Myriad Genetics Inc., Salt Lake City, UT 84108, USA.

出版信息

J Biomed Biotechnol. 2010;2010. doi: 10.1155/2010/386870. Epub 2010 Jul 8.


DOI:10.1155/2010/386870
PMID:20706610
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2914423/
Abstract

Genomic copy number variations are a typical feature of cancer. These variations may influence cancer outcomes as well as effectiveness of treatment. There are many computational methods developed to detect regions with deletions and amplifications without estimating actual copy numbers (CN) in these regions. We have developed a computational method capable of detecting regions with deletions and amplifications as well as estimating actual copy numbers in these regions. The method is based on determining how signal intensity from different probes is related to CN, taking into account changes in the total genome size, and incorporating into analysis contamination of the solid tumors with benign tissue. Hidden Markov Model is used to obtain the most likely CN solution. The method has been implemented for Affymetrix 500K GeneChip arrays and Agilent 244K oligonucleotide arrays. The results of CN analysis for normal cell lines, cancer cell lines, and tumor samples are presented. The method is capable of detecting copy number alterations in tumor samples with up to 80% contamination with benign tissue. Analysis of 178 cancer cell lines reveals multiple regions of common homozygous deletions and strong amplifications encompassing known tumor suppressor genes and oncogenes as well as novel cancer related genes.

摘要

基因组拷贝数变异是癌症的一个典型特征。这些变异可能会影响癌症的预后以及治疗效果。已经开发出许多计算方法来检测存在缺失和扩增的区域,而无需估计这些区域的实际拷贝数(CN)。我们开发了一种计算方法,它能够检测存在缺失和扩增的区域,并能估计这些区域的实际拷贝数。该方法基于确定来自不同探针的信号强度如何与拷贝数相关,同时考虑到全基因组大小的变化,并将良性组织对实体瘤的污染纳入分析。使用隐马尔可夫模型来获得最可能的拷贝数解决方案。该方法已应用于Affymetrix 500K基因芯片阵列和安捷伦244K寡核苷酸阵列。文中展示了对正常细胞系、癌细胞系和肿瘤样本进行拷贝数分析的结果。该方法能够检测出含有高达80%良性组织污染的肿瘤样本中的拷贝数改变。对178个癌细胞系的分析揭示了多个常见纯合缺失和强烈扩增区域,这些区域包含已知的肿瘤抑制基因和癌基因以及新的癌症相关基因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18c0/2914423/a0477f774f61/JBB2010-386870.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18c0/2914423/817d31a80319/JBB2010-386870.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18c0/2914423/d0ce5ef5b8cd/JBB2010-386870.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18c0/2914423/cc9d25f1ccf1/JBB2010-386870.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18c0/2914423/a0477f774f61/JBB2010-386870.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18c0/2914423/817d31a80319/JBB2010-386870.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18c0/2914423/d0ce5ef5b8cd/JBB2010-386870.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18c0/2914423/cc9d25f1ccf1/JBB2010-386870.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18c0/2914423/a0477f774f61/JBB2010-386870.004.jpg

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[1]
Computational method for estimating DNA copy numbers in normal samples, cancer cell lines, and solid tumors using array comparative genomic hybridization.

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本文引用的文献

[1]
Molecular classification of solid tumours: towards pathway-driven therapeutics.

Br J Cancer. 2009-5-19

[2]
Phenotype and 244k array-CGH characterization of chromosome 13q deletions: an update of the phenotypic map of 13q21.1-qter.

Am J Med Genet A. 2009-5

[3]
Detection of submicroscopic constitutional chromosome aberrations in clinical diagnostics: a validation of the practical performance of different array platforms.

Eur J Hum Genet. 2008-7

[4]
Computational methods for the analysis of array comparative genomic hybridization.

Cancer Inform. 2007-2-10

[5]
Genomic DNA pooling for whole-genome association scans in complex disease: empirical demonstration of efficacy in rheumatoid arthritis.

Genes Immun. 2007-1

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Am J Hum Genet. 2005-10

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Proc Natl Acad Sci U S A. 2004-12-21

[9]
The RAB25 small GTPase determines aggressiveness of ovarian and breast cancers.

Nat Med. 2004-11

[10]
EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib.

Proc Natl Acad Sci U S A. 2004-9-7

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