Clonality of lobular carcinoma in situ and synchronous invasive lobular carcinoma
Clonality of lobular carcinoma in situ and synchronous invasive lobular carcinoma
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DOI：
10.1002/cncr.20273
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发表时间：
2004-06-12
期刊：
影响因子：
6.2
通讯作者：
Waldman, FM
中科院分区：
文献类型：
--
作者：
Hwang, ES;Nyante, SJ;Waldman, FM
背景乳腺小叶原位癌（LCIS）被认为是双侧乳腺癌风险增加的标志物。然而，LCIS与浸润性小叶癌（ILC）的频繁相关性提示了一种代谢产物关系。采用基于芯片的比较基因组杂交（CGH）技术，分析同步LCIS和3 ILC之间可能的基因组关系。从加州大学旧金山分校弗朗西斯科病理档案中识别出24个包含同步LCIS和ILC的样本。使用随机引物扩增的显微切割DNA进行阵列CGH。将样品杂交到由约2400个克隆组成的细菌人工染色体阵列上。比较同步LCIS和2 ILC内的改变模式。在3例LCIS和ILC的样本中，基因组的很大一部分发生了改变。最常见的变化是1q的增加和16q的丢失，这两种变化通常都是以整臂变化的形式发生的。在其他染色体臂上观察到较小的增益和损失4区域。14例LCIS与其配对的ILC样本的相关性高于与任何其他ILC的相关性，如加权相似性评分所示。LCIS和ILC是表现出一系列基因组改变的肿瘤性病变。在目前的研究中，同步LCIS和ILC之间的遗传关系表明，在大多数配对标本的克隆性。这些数据与从LCIS到ILC的进展途径一致。作者得出结论，LCIS是允许瘤形成的环境的标志物，其本身可能代表浸润性癌的前兆。(C)2004年美国癌症协会。
BACKGROUND. Lobular carcinoma in situ (LCIS) of the breast is considered a marker for an increased risk of carcinoma in both breasts. However, the frequent association of LCIS with invasive lobular carcinoma (ILC) suggests a precursor-product relation. The possible genomic relation between synchronous LCIS and 3 ILC was analyzed using the technique of array-based comparative genomic hybridization (CGH).METHODS. Twenty-four samples from the University of California-San Francisco pathology archives that contained synchronous LCIS and ILC were identified. Array CGH was performed using random primer-amplified microdissected DNA. Samples were hybridized onto bacterial artificial chromosome arrays composed of approximately 2400 clones. Patterns of alterations within synchronous LCIS and 2 ILC were compared.RESULTS. A substantial proportion of the genome was altered in samples of both 3 LCIS and ILC. The most frequent alterations were gain of 1q and loss of 16q, both of which usually occurred as whole-arm changes. Smaller regions of gain and loss 4 were seen on other chromosome arms. Fourteen samples of LCIS were related more to their paired samples of ILC than to any other ILC, as demonstrated by a weighted similarity score.CONCLUSIONS. LCIS and ILC are neoplastic lesions that demonstrate a range of genomic alterations. In the current study, the genetic relation between synchronous LCIS and ILC suggested clonality in a majority of the paired specimens. These data were consistent with a progression pathway from LCIS to ILC. The authors conclude that LCIS, which is known to be a marker for an environment that is permissive of neoplasia, may itself represent a precursor to invasive carcinoma. (C) 2004 American Cancer Society.