Patterns of chromosomal alterations in breast ductal carcinoma in situ
Patterns of chromosomal alterations in breast ductal carcinoma in situ
复制标题
DOI：
10.1158/1078-0432.ccr-04-0165
复制
发表时间：
2004-08-01
影响因子：
11.5
通讯作者：
Waldman, FM
中科院分区：
文献类型：
--
作者：
Hwang, ES;DeVries, S;Waldman, FM
目的：导管原位癌（DCIS）被认为是浸润性癌的非专性先兆。纯DCIS与侵袭性癌症特有的基因组变化，以及个体DCIS亚型特有的改变尚未完全定义。实验设计：应用比较基因组杂交技术检测34例单纯性导管内癌的染色体拷贝数改变，并与12例配对的同时性导管内癌和浸润性导管癌进行比较，以及另外146例导管或小叶组织学浸润性乳腺癌。高级别和低/中级DCIS之间的基因组差异，以及纯DCIS和浸润性癌之间的差异，被identified.Results：纯DCIS表现出几乎相同程度的染色体不稳定性浸润性导管癌。低/中级别DCIS与高级别DCIS相比，16 q丢失的比例更高（分别为65%与12%; P = 0.002）。与低级别DCIS相比，高级别DCIS表现出更频繁的17 q增益（65 vs 41%; P 0.15）和更高的8 p频率丢失（77 vs 41%; P 0.04）。在这些情况下，与同步DCIS和浸润性导管癌的染色体改变表现出高度的共享变化内的两个component.Conclusions：DCIS是遗传先进的，表现出类似程度的染色体改变浸润性导管癌。高级别和低/中级别DCIS之间的改变模式不同，支持不同组织学级别DCIS与不同基因组变化相关的模型。这些染色体改变区域可能是治疗的潜在靶点和/或预后标志物。
Purpose: Ductal carcinoma in situ (DCIS) is thought to be a nonobligate precursor of invasive cancer. Genomic changes specific to pure DCIS versus invasive cancer, as well as alterations unique to individual DCIS subtypes, have not been fully defined.Experimental Design: Chromosomal copy number alterations were examined by comparative genomic hybridization in 34 cases of pure DCIS and compared with 12 cases of paired synchronous DCIS and invasive ductal cancer, as well as to 146 additional cases of invasive breast cancer of ductal or lobular histology. Genomic differences between high-grade and low/intermediate-grade DCIS, as well as between pure DCIS and invasive cancer, were identified.Results: Pure DCIS showed almost the same degree of chromosomal instability as invasive ductal cancers. A higher proportion of low/intermediate-grade versus high-grade DCIS had loss of 16q (65 versus 12%, respectively; P = 0.002). When compared with lower grade DCIS, high-grade DCIS exhibited more frequent gain of 17q (65 versus 41%; P 0.15) and higher frequency loss of 8p (77 versus 41%; P 0.04). Chromosomal alterations in those cases with synchronous DCIS and invasive ductal cancer showed a high degree of shared changes within the two components.Conclusions: DCIS is genetically advanced, showing a similar degree of chromosomal alterations as invasive ductal cancer. The pattern of alterations differed between high-and low/intermediate-grade DCIS, supporting a model in which different histological grades of DCIS are associated with distinct genomic changes. These regions of chromosomal alterations may be potential targets for treatment and/or markers of prognosis.