Genomic profiling of multiple breast cancer reveals inter-lesional heterogeneity
Genomic profiling of multiple breast cancer reveals inter-lesional heterogeneity
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DOI：
10.1038/s41416-019-0713-1
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发表时间：
2020-01-13
影响因子：
8.8
通讯作者：
Park, So Yeon
中科院分区：
文献类型：
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作者：
Ahn, Soomin;Kim, Hyun Jeong;Park, So Yeon
背景乳腺癌的多发性是常见的。对多种乳腺癌的研究显示，个体病变之间的生物标志物状态具有高度一致性。然而，多个病变之间的基因组差异还没有得到很好的确定。我们的目的是调查潜在的基因组异质性的多发性乳腺癌。方法21例经病理证实的乳腺多发癌患者，均经手术病理证实。从21例患者中选择两个病灶，并评价每个病灶的生物标志物状态。使用由170个基因组成的癌症基因组进行基于捕获的靶向下一代测序。结果21例患者中有2例（10%）内在亚型不一致。在21例患者中的13例中检测到致病性突变，其中11例在两个病变中共有致癌变异。其余2例患者产生了TP53、ATM和PIK3CA的不同突变结果。在21例患者中的7例（33%）中观察到拷贝数改变的差异，包括ERBB 2（n = 2）、FGFR 1（n = 2）和FGFR 2（n = 1）基因。结论尽管单个肿瘤的组织学特征相似，但超过三分之一的患者存在肿瘤间基因组差异。在多个乳腺癌中进行基因组检测时，需要考虑病变间的基因组异质性。
Background Multiplicity in breast cancer is common. Studies on multiple breast cancers have revealed high concordance in biomarker status among individual lesions. However, genomic differences among multiple lesions are not well-established. We aimed to investigate the potential genomic heterogeneity of multiple breast cancer. Methods Twenty-one patients with radiologically and histologically evident multiple breast cancer with similar histology were included. Two lesions from each of the 21 patients were selected, and biomarker status was evaluated for each lesion. Capture-based targeted next-generation sequencing was performed using a cancer gene panel consisting of 170 genes. Results We identified discordance in intrinsic subtype in 2 (10%) of the 21 patients. Pathogenic mutations were detected in 13 of the 21 patients, of whom 11 shared oncogenic variants in the two lesions. The remaining two patients yielded different mutation results for TP53, ATM, and PIK3CA. Difference in copy number alteration was observed in 7 (33%) of the 21 patients including ERBB2 (n = 2), FGFR1 (n = 2), and FGFR2 (n = 1) genes. Conclusion Despite similar histologic features of the individual lesions, inter-lesional genomic difference was identified in more than one-third of the patients. Inter-lesional genomic heterogeneity needs to be considered when performing a genomic test in multiple breast cancers.