Exome sequencing of contralateral breast cancer identifies metastatic disease
Exome sequencing of contralateral breast cancer identifies metastatic disease
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DOI：
10.1007/s10549-015-3403-6
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发表时间：
2015-06-01
影响因子：
3.8
通讯作者：
Czene, Kamila
中科院分区：
文献类型：
--
作者：
Klevebring, Daniel;Lindberg, Johan;Czene, Kamila
患对侧乳腺癌（CBC）的女性与患单侧乳腺癌的女性相比，预后明显较差。CBC患者预后不良的一个可能解释是，在一个患者亚组中，第二种癌症不是新的原发性肿瘤，而是第一种癌症的转移，通过选择治疗可能获得侵袭性特征。实体瘤的外显子组和全基因组测序先前已用于研究几种疾病中原发性肿瘤和转移瘤之间的克隆关系。为了评估第一种和第二种癌症之间的关系，我们进行了外显子组测序，以确定第一种和第二种癌症中的体细胞突变，并比较了25例异时CBC患者的配对正常组织。对于三名患者，我们鉴定了共同的体细胞突变，表明共同的克隆起源，从而证明第二个肿瘤是第一个癌症的转移，而不是新的原发性癌症。因此，这些患者均在第二次诊断后3年内发生远处转移，而22例非共享体细胞特征的患者中有7例发生远处转移。两种肿瘤的基因组分析有助于临床医生区分真正的CBC和随后的转移。
Women with contralateral breast cancer (CBC) have significantly worse prognosis compared to women with unilateral cancer. A possible explanation of the poor prognosis of patients with CBC is that in a subset of patients, the second cancer is not a new primary tumor but a metastasis of the first cancer that has potentially obtained aggressive characteristics through selection of treatment. Exome and whole-genome sequencing of solid tumors has previously been used to investigate the clonal relationship between primary tumors and metastases in several diseases. In order to assess the relationship between the first and the second cancer, we performed exome sequencing to identify somatic mutations in both first and second cancers, and compared paired normal tissue of 25 patients with metachronous CBC. For three patients, we identified shared somatic mutations indicating a common clonal origin thereby demonstrating that the second tumor is a metastasis of the first cancer, rather than a new primary cancer. Accordingly, these patients all developed distant metastasis within 3 years of the second diagnosis, compared with 7 out of 22 patients with non-shared somatic profiles. Genomic profiling of both tumors help the clinicians distinguish between true CBCs and subsequent metastases.