Comparative genomic analysis reveals bilateral breast cancers are genetically independent.
Comparative genomic analysis reveals bilateral breast cancers are genetically independent.
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比较基因组分析显示双侧乳腺癌在遗传上是独立的
DOI：
10.18632/oncotarget.5569
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发表时间：
2015-10-13
期刊：
影响因子：
--
通讯作者：
Chen K
中科院分区：
文献类型：
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作者：
Song F;Li X;Song F;Zhao Y;Li H;Zheng H;Gao Z;Wang J;Zhang W;Chen K
双侧乳腺癌（BBC）构成了一个重大的挑战，肿瘤学家，因为这两个病变之间的神秘关系。本研究的目的是确定对侧乳腺癌的起源（依赖或独立于索引肿瘤）。在这里，我们使用超深全外显子组测序和阵列比较基因组杂交（aCGH）来研究具有不同肿瘤亚型和每个肿瘤发展之间的时间间隔的四对BBC样本。我们使用两对原发性乳腺肿瘤和相应的转移性肝脏病变作为对照。我们用三种方法测试了BBC的起源独立性：突变一致性、突变特征聚类和使用拷贝数谱的克隆性分析。我们发现配对的BBC样本具有接近零的一致突变率，其远低于配对的原发/转移样本。突变特征分析的结果也表明，BBC是相互独立的。使用aCGH数据的克隆性分析进一步揭示了配对的BBC样品是克隆独立的，与配对的原发/转移样品中发现的克隆相关起源相反。我们的初步研究结果表明，在中国汉族妇女的BBCs是起源独立的，因此应单独对待。
Bilateral breast cancer (BBC) poses a major challenge for oncologists because of the cryptic relationship between the two lesions. The purpose of this study was to determine the origin of the contralateral breast cancer (either dependent or independent of the index tumor). Here, we used ultra-deep whole-exome sequencing and array comparative genomic hybridization (aCGH) to study four paired samples of BBCs with different tumor subtypes and time intervals between the developments of each tumor. We used two paired primary breast tumors and corresponding metastatic liver lesions as the control. We tested the origin independent nature of BBC in three ways: mutational concordance, mutational signature clustering, and clonality analysis using copy number profiles. We found that the paired BBC samples had near-zero concordant mutation rates, which were much lower than those of the paired primary/metastasis samples. The results of a mutational signature analysis also suggested that BBCs are independent of one another. A clonality analysis using aCGH data further revealed that paired BBC samples was clonally independent, in contrast to clonal related origin found for paired primary/metastasis samples. Our preliminary findings show that BBCs in Han Chinese women are origin independent and thus should be treated separately.