Integrative analysis of genomic aberrations associated with prostate cancer progression
Integrative analysis of genomic aberrations associated with prostate cancer progression
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DOI：
10.1158/0008-5472.can-07-1297
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发表时间：
2007-09-01
期刊：
影响因子：
11.2
通讯作者：
Chinnaiyan, Arul M.
中科院分区：
文献类型：
--
作者：
Kim, Jung H.;Dhanasekaran, Saravana M.;Chinnaiyan, Arul M.
在转录组改变的背景下对基因组畸变进行综合分析将导致对前列腺癌进展的更全面的观点。全基因组拷贝数的变化进行了监测，使用阵列比较基因组杂交的激光捕获显微切割的前列腺癌样本跨越前列腺癌进展的阶段，包括前体病变，临床局部疾病，和转移性疾病。对来自38名患者的总共62个特定细胞群进行了分析。定义了每种样本类型的最小共同区（MCR）变化，转移性样本显示最多的变化。就改变区域的大小和受影响基因的数量而言，具有高格里森等级的临床局部前列腺癌样本与转移性样本相似。在假定的前体病变（高级别前列腺上皮内瘤变（PIN））中，13例MCR中共有9例与前列腺癌病例重叠（3q 29、5q31.3-q32、6 q27和8q24.3中的扩增和6q22.31、16p12.2、17q21.2和17q21.31中的缺失），而萎缩后增生（PAH）没有表现出这种重叠。有趣的是，不过表达ETS家族成员的前列腺癌（即，基因融合阴性前列腺癌）在1 q23、6 q16、6 q21、10 q23和10 q24中具有差异畸变。与匹配的mRNA谱的综合分析确定了在前列腺癌进展中涉及的几个拟议的候选基因的遗传改变。
Integrative analysis of genomic aberrations in the context of trancriptomic alterations will lead to a more comprehensive perspective on prostate cancer progression. Genome-wide copy number changes were monitored using array comparative genomic hybridization of laser-capture microdissected prostate cancer samples spanning stages of prostate cancer progression, including precursor lesions, clinically localized disease, and metastatic disease. A total of 62 specific cell populations from 38 patients were profiled. Minimal common regions (MCR) of alterations were defined for each sample type, and metastatic samples displayed the most number of alterations. Clinically localized prostate cancer samples with high Gleason grade resembled metastatic samples with respect to the size of altered regions and number of affected genes. A total of 9 out of 13 MCRs in the putative precursor lesion, high-grade prostatic intraepithelial neoplasia (PIN), showed an overlap with prostate cancer cases (amplifications in 3q29, 5q31.3-q32, 6q27, and 8q24.3 and deletions in 6q22.31, 16p 12.2, 17q21.2, and 17q21.31), whereas postatrophic hyperplasia (PAH) did not exhibit this overlap. Interestingly, prostate cancers that do not overexpress ETS family members (i.e., gene fusion-negative prostate cancers) harbor differential aberrations in 1q23, 6q16, 6q21, 10q23, and 10q24. Integrative analysis with matched mRNA profiles identified genetic alterations in several proposed candidate genes implicated in prostate cancer progression.