Genomic profiling of histological special types of breast cancer
Genomic profiling of histological special types of breast cancer
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DOI：
10.1007/s10549-013-2740-6
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发表时间：
2013-11-01
影响因子：
3.8
通讯作者：
Reis-Filho, Jorge S.
中科院分区：
文献类型：
--
作者：
Horlings, Hugo M.;Weigelt, Britta;Reis-Filho, Jorge S.
组织学特殊类型的乳腺癌具有独特的形态学特征，占所有浸润性乳腺癌的25%。我们试图确定在基因组水平上，组织学特殊类型的乳腺癌是否与分级和雌激素受体（ER）匹配的无特殊类型的浸润性癌（IC-NSTs）不同，并确定组织学特殊类型乳腺癌中表达与基因拷贝数相关的基因。我们使用基于阵列的比较基因组杂交（aCGH）对10种组织学特殊类型的59例乳腺癌进行了特征分析。分层聚类表明，基因拷贝数畸变模式与er状态和组织学分级分离，并且每种乳腺癌组织学特殊类型的样本优先聚类在一起。我们证实了先前报道的小叶癌、微乳头癌、化生癌和黏液癌的基因拷贝数畸变模式。另一方面，发现化生癌和髓样癌具有与分级和er匹配的ic - nst相似的基因组图谱。在具有破骨细胞样基质巨细胞的侵袭性癌中观察到的基因组畸变支持其分类为IC-NST变体。综合aCGH和基因表达分析鉴定出145个转录本，当在组织学特殊类型的乳腺癌中扩增时，这些转录本显着过表达。我们的研究结果表明，除了组织学分级和er状态外，组织学类型也与乳腺癌中基因拷贝数畸变的模式和复杂性有关，腺样囊性癌和黏液性癌是er阴性和er阳性乳腺癌的例子，它们具有不同的基因拷贝数畸变谱。
Histological special types of breast cancer have distinctive morphological features and account for up to 25 % of all invasive breast cancers. We sought to determine whether at the genomic level, histological special types of breast cancer are distinct from grade- and estrogen receptor (ER)-matched invasive carcinomas of no special type (IC-NSTs), and to define genes whose expression correlates with gene copy number in histological special types of breast cancer. We characterized 59 breast cancers of ten histological special types using array-based comparative genomic hybridization (aCGH). Hierarchical clustering revealed that the patterns of gene copy number aberrations segregated with ER-status and histological grade, and that samples from each of the breast cancer histological special types preferentially clustered together. We confirmed the patterns of gene copy number aberrations previously reported for lobular, micropapillary, metaplastic, and mucinous carcinomas. On the other hand, metaplastic and medullary carcinomas were found to have genomic profiles similar to those of grade- and ER-matched IC-NSTs. The genomic aberrations observed in invasive carcinomas with osteoclast-like stromal giant cells support its classification as IC-NST variant. Integrative aCGH and gene expression analysis led to the identification of 145 transcripts that were significantly overexpressed when amplified in histological special types of breast cancer. Our results illustrate that together with histological grade and ER-status, histological type is also associated with the patterns and complexity of gene copy number aberrations in breast cancer, with adenoid cystic and mucinous carcinomas being examples of ER-negative and ER-positive breast cancers with distinctive repertoires of gene copy number aberrations.