Metastatic drivers same as primary Treatment decisions for cancer patients are increasingly guided by analysis of the gene mutations that drive primary tumor growth. Relatively little is known about driver gene mutations in metastases, which cause most cancer-related deaths. Reiter et al. explored whether the growth of different metastatic lesions within an individual patient is fueled by the same or distinct gene mutations. In a study of 76 untreated metastases from 20 patients with different types of cancer, all metastases within a patient shared the same functional driver gene mutations. Thus, analysis of a single biopsy could help oncologists select the optimal therapy for patients with widespread metastatic disease. Science, this issue p. 1033 The growth of different metastatic lesions within an individual cancer patient is fueled by the same genetic mutations. Metastases are responsible for the majority of cancer-related deaths. Although genomic heterogeneity within primary tumors is associated with relapse, heterogeneity among treatment-naïve metastases has not been comprehensively assessed. We analyzed sequencing data for 76 untreated metastases from 20 patients and inferred cancer phylogenies for breast, colorectal, endometrial, gastric, lung, melanoma, pancreatic, and prostate cancers. We found that within individual patients, a large majority of driver gene mutations are common to all metastases. Further analysis revealed that the driver gene mutations that were not shared by all metastases are unlikely to have functional consequences. A mathematical model of tumor evolution and metastasis formation provides an explanation for the observed driver gene homogeneity. Thus, single biopsies capture most of the functionally important mutations in metastases and therefore provide essential information for therapeutic decision-making.

中文翻译：

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未治疗转移瘤中最小的功能驱动基因异质性

转移驱动因素与原发肿瘤患者的主要治疗决策越来越多地受到驱动原发肿瘤生长的基因突变分析的指导。人们对转移灶中的驱动基因突变知之甚少，转移灶导致大多数癌症相关死亡。瑞特等人。探讨了个体患者内不同转移性病变的生长是否由相同或不同的基因突变推动。在一项针对 20 名不同类型癌症患者的 76 例未经治疗的转移瘤的研究中，一名患者的所有转移瘤都具有相同的功能驱动基因突变。因此，对单次活检的分析可以帮助肿瘤学家为广泛转移性疾病的患者选择最佳疗法。科学，这个问题 p。1033 单个癌症患者体内不同转移性病变的生长是由相同的基因突变推动的。大多数与癌症相关的死亡都是由转移引起的。尽管原发肿瘤内的基因组异质性与复发有关，但尚未对初治转移瘤的异质性进行全面评估。我们分析了来自 20 名患者的 76 个未治疗转移的测序数据，并推断出乳腺癌、结肠直肠癌、子宫内膜癌、胃癌、肺癌、黑色素瘤、胰腺癌和前列腺癌的癌症系统发育。我们发现，在个体患者中，绝大多数驱动基因突变对于所有转移灶都是常见的。进一步的分析表明，并非所有转移都共享的驱动基因突变不太可能产生功能性后果。肿瘤进化和转移形成的数学模型为观察到的驱动基因同质性提供了解释。因此，单次活检捕获了转移中大多数功能上重要的突变，因此为治疗决策提供了必要的信息。