The molecular pathology of breast cancer progression.
The molecular pathology of breast cancer progression.
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DOI：
10.1002/path.2808
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发表时间：
2011-01
影响因子：
7.3
通讯作者：
Sgroi, Dennis C.
中科院分区：
文献类型：
--
作者：
Bombonati, Alessandro;Sgroi, Dennis C.
关键词：
目前的人类乳腺癌进展模型提出了一个线性的多步骤过程，从扁平上皮异型增生（FEA）开始，发展到非典型导管增生（ADH），发展到DCIS，最终达到侵袭性导管癌的潜在致死阶段。几十年来，人类乳腺癌研究的一个主要挑战是确定与乳腺癌进展不同阶段相关的分子变化。直到最近，实现这一目标的进展一直受到技术限制的阻碍，这些限制与将先进的分子技术应用于乳腺肿瘤发生的微观侵袭前阶段有关。综合、高通量遗传学、转录组学和表观遗传学技术的最新进展，结合先进的显微解剖和离体分离技术，为更全面地了解人类乳腺癌进化不同阶段复杂的分子遗传学和分子生物学相互关系提供了基础。在这里，我们回顾了分子生物学数据，表明乳腺癌的发展和演变沿着两个不同的分子遗传途径。我们还简要回顾了基因表达和表观遗传学数据，这些数据支持肿瘤微环境在人类乳腺肿瘤发生过程中是一个重要的同谋者，而不是一个被动的旁观者。
The current model of human breast cancer progression proposes a linear multistep process which initiates as flat epithelial atypia (FEA), progresses to atypical ductal hyperplasia (ADH), evolves into DCIS, and culminates in the potentially lethal stage of invasive ductal carcinoma. For several decades a major challenge to human breast cancer research has been the identification of the molecular alterations associated with the different stages of breast cancer progression. Until recently, progress in attaining this goal has been hampered by technical limitations associated with applying advanced molecular technologies to the microscopic preinvasive stages of breast tumorigenesis. Recent advances in comprehensive, high-throughput genetic, transcriptomic and epigenetic technologies in combination with advanced microdissection and ex vivo isolation techniques have provided for a more complete understanding of the complex molecular genetic and molecular biological inter-relationship of the different stages of human breast cancer evolution. Here we review the molecular biological data that suggest breast cancer develops and evolves along two distinct molecular genetic pathways. We also briefly review gene expression and epigenetic data that support the view of the tumor microenvironment as an important coconspirator rather than a passive bystander during human breast tumorigenesis.
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