De Mattos-Arruda Leticia, Mayor Regina, Ng Charlotte K Y, Weigelt Britta, Martínez-Ricarte Francisco, Torrejon Davis, Oliveira Mafalda, Arias Alexandra, Raventos Carolina, Tang Jiabin, Guerini-Rocco Elena, Martínez-Sáez Elena, Lois Sergio, Marín Oscar, de la Cruz Xavier, Piscuoglio Salvatore, Towers Russel, Vivancos Ana, Peg Vicente, Ramon y Cajal Santiago, Carles Joan, Rodon Jordi, González-Cao María, Tabernero Josep, Felip Enriqueta, Sahuquillo Joan, Berger Michael F, Cortes Javier, Reis-Filho Jorge S, Seoane Joan
Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, P. Vall d'Hebron 119-129, 08035 Barcelona, Spain.
Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.
Nat Commun. 2015 Nov 10;6:8839. doi: 10.1038/ncomms9839.
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.
血浆中的游离循环肿瘤DNA(ctDNA)已被证明能反映肿瘤中存在的基因组改变,并已用于监测肿瘤进展和治疗反应。然而,脑肿瘤患者血浆中不存在或仅存在少量ctDNA,这使得无法通过血浆ctDNA对脑癌进行基因组特征分析。在此,我们表明源自中枢神经系统肿瘤的ctDNA在脑脊液(CSF)中的含量比在血浆中更为丰富。与血浆相比,对脑脊液ctDNA进行大规模平行测序能更全面地表征脑肿瘤的基因组改变,从而能够识别可用于指导治疗的脑肿瘤体细胞突变。我们发现脑脊液ctDNA水平会随时间纵向波动,并与脑肿瘤负荷的变化一致,可作为监测脑恶性肿瘤的生物标志物。此外,脑脊液ctDNA还被证明有助于并补充软脑膜癌病的诊断。