颜林林
(2022-06-13 05:47):
#paper doi:10.1038/s41588-022-01082-3 Nature Genetics, 2022, Genomic analysis defines clonal relationships of ductal carcinoma in situ and recurrent invasive breast cancer. 本文研究导管原位癌（DCIS）。该疾病常见于乳腺癌筛查，即使经过治疗，也仍然有小部分患者会恶化复发成为浸润性乳腺癌。本文试图研究，恶化的这些患者，是否都来自原发性DCIS的复发克隆，亦或仅是新发的无关疾病。为此，本研究纳入了129对DCIS复发病例样本（即原位DCIS样本和复发样本；同时也包含匹配的癌旁对照组织），通过开展全外显子组测序、SNP芯片检测或靶向基因组panel测序（这里技术平台方法存在差别，是因为样本及其实验，分别来自和开展于荷兰、英国和美国的三家不同单位），进行基因组突变分析和拷贝数变异分析。同时也从中选取了4例病例，将其原发与复发组织，分别进行解离并开展单细胞基因组测序。针对这两种策略，都分别进行了克隆演化分析，最终确认并非所有同侧浸润性乳腺癌都与先前的 DCIS 有克隆相关性，其中有约五分之一其实为新发原发性癌症。此结果也在更大范围且更详细的程度上，验证了前人的研究结果。
Genomic analysis defines clonal relationships of ductal carcinoma in situ and recurrent invasive breast cancer
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Abstract:
Ductal carcinoma in situ (DCIS) is the most common form of preinvasive breast cancer and, despite treatment, a small fraction (5-10%) of DCIS patients develop subsequent invasive disease. A fundamental biologic question is whether the invasive disease arises from tumor cells in the initial DCIS or represents new unrelated disease. To address this question, we performed genomic analyses on the initial DCIS lesion and paired invasive recurrent tumors in 95 patients together with single-cell DNA sequencing in a subset of cases. Our data show that in 75% of cases the invasive recurrence was clonally related to the initial DCIS, suggesting that tumor cells were not eliminated during the initial treatment. Surprisingly, however, 18% were clonally unrelated to the DCIS, representing new independent lineages and 7% of cases were ambiguous. This knowledge is essential for accurate risk evaluation of DCIS, treatment de-escalation strategies and the identification of predictive biomarkers.
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