Cerebrospinal fluid-derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma.
Cerebrospinal fluid-derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma.
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DOI：
10.1038/ncomms9839
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发表时间：
2015-11-10
影响因子：
16.6
通讯作者：
Seoane J
中科院分区：
文献类型：
--
作者：
De Mattos-Arruda L;Mayor R;Ng CKY;Weigelt B;Martínez-Ricarte F;Torrejon D;Oliveira M;Arias A;Raventos C;Tang J;Guerini-Rocco E;Martínez-Sáez E;Lois S;Marín O;de la Cruz X;Piscuoglio S;Towers R;Vivancos A;Peg V;Ramon y Cajal S;Carles J;Rodon J;González-Cao M;Tabernero J;Felip E;Sahuquillo J;Berger MF;Cortes J;Reis-Filho JS;Seoane J
血浆中的无细胞循环肿瘤DNA（ctDNA）已被证明是肿瘤中存在的基因组改变的信息，并已被用于监测肿瘤进展和对治疗的反应。然而，患有脑肿瘤的患者在血浆中不存在或存在少量ctDNA，从而排除了通过血浆ctDNA对脑癌的基因组表征。在这里，我们表明，来自中枢神经系统肿瘤的ctDNA是更丰富的存在于脑脊液（CSF）比在血浆中。CSF ctDNA的大规模平行测序比血浆更全面地表征脑肿瘤的基因组改变，从而允许鉴定可操作的脑肿瘤体细胞突变。我们发现CSF ctDNA水平随时间纵向波动，并遵循脑肿瘤负荷的变化，提供生物标志物来监测脑恶性肿瘤。此外，CSF ctDNA被证明可以促进和补充软脑膜癌病的诊断。 癌症患者血浆中循环的DNA携带原发性肿瘤的特征，然而在脑癌患者中发现这种DNA的水平较低。在这里，作者表明，循环肿瘤DNA可以在癌症患者的脑脊液中检测到，与血浆中的DNA相比，这更好地概括了原发性肿瘤。
Cell-free circulating tumour DNA (ctDNA) in plasma has been shown to be informative of the genomic alterations present in tumours and has been used to monitor tumour progression and response to treatments. However, patients with brain tumours do not present with or present with low amounts of ctDNA in plasma precluding the genomic characterization of brain cancer through plasma ctDNA. Here we show that ctDNA derived from central nervous system tumours is more abundantly present in the cerebrospinal fluid (CSF) than in plasma. Massively parallel sequencing of CSF ctDNA more comprehensively characterizes the genomic alterations of brain tumours than plasma, allowing the identification of actionable brain tumour somatic mutations. We show that CSF ctDNA levels longitudinally fluctuate in time and follow the changes in brain tumour burden providing biomarkers to monitor brain malignancies. Moreover, CSF ctDNA is shown to facilitate and complement the diagnosis of leptomeningeal carcinomatosis. DNA circulating in the plasma of cancer patients carries features of the primary tumour, however such DNA is found in low levels in brain cancer patients. Here, the authors show that circulating tumour DNA can be detected in the cerebral spinal fluid of cancer patients and that this better recapitulates the primary tumour compared to DNA from the plasma.