Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, 0310 Oslo, Norway.
Division of Pathology, Oslo University Hospital Radiumhospitalet, 0310 Oslo, Norway.
Sci Transl Med. 2010 Jun 30;2(38):38ra47. doi: 10.1126/scitranslmed.3000611.
Distinct molecular subtypes of breast carcinomas have been identified, but translation into clinical use has been limited. We have developed two platform-independent algorithms to explore genomic architectural distortion using array comparative genomic hybridization data to measure (i) whole-arm gains and losses [whole-arm aberration index (WAAI)] and (ii) complex rearrangements [complex arm aberration index (CAAI)]. By applying CAAI and WAAI to data from 595 breast cancer patients, we were able to separate the cases into eight subgroups with different distributions of genomic distortion. Within each subgroup data from expression analyses, sequencing and ploidy indicated that progression occurs along separate paths into more complex genotypes. Histological grade had prognostic impact only in the luminal-related groups, whereas the complexity identified by CAAI had an overall independent prognostic power. This study emphasizes the relation among structural genomic alterations, molecular subtype, and clinical behavior and shows that objective score of genomic complexity (CAAI) is an independent prognostic marker in breast cancer.
已经确定了不同的乳腺癌分子亚型,但将其转化为临床应用受到限制。我们开发了两种与平台无关的算法,使用阵列比较基因组杂交数据来探索基因组结构的扭曲,以测量 (i) 整条臂的增益和缺失[整条臂异常指数 (WAAI)]和 (ii) 复杂重排[复杂臂异常指数 (CAAI)]。通过将 CAAI 和 WAAI 应用于 595 名乳腺癌患者的数据,我们能够将病例分为八个具有不同基因组扭曲分布的亚组。在每个亚组中,来自表达分析、测序和倍性的数据表明,进展是沿着不同的路径进入更复杂的基因型。组织学分级仅在 luminal 相关组中具有预后影响,而 CAAI 确定的复杂性具有整体独立的预后能力。本研究强调了结构基因组改变、分子亚型和临床行为之间的关系,并表明基因组复杂性的客观评分 (CAAI) 是乳腺癌的独立预后标志物。