Cerebrospinal fluid-derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma
Leticia De Mattos-Arruda,Leticia De Mattos-Arruda,Leticia De Mattos-Arruda,Regina Mayor,Charlotte K.Y. Ng,Britta Weigelt,Francisco Martínez-Ricarte,Francisco Martínez-Ricarte,Davis Y. Torrejon,Mafalda Oliveira,Alexandra Arias,C. Raventós,Jiabin Tang,Elena Guerini-Rocco,Elena Martínez-Sáez,Sergio Lois,Oscar Marín,Xavier de la Cruz,Xavier de la Cruz,Salvatore Piscuoglio,Russel Towers,Ana Vivancos,Vicente Peg,Santiago Ramón y Cajal,Santiago Ramón y Cajal,Joan Carles,Jordi Rodon,Maria Gonzalez-Cao,Josep Tabernero,Josep Tabernero,Enriqueta Felip,Enriqueta Felip,Joan Sahuquillo,Joan Sahuquillo,Michael F. Berger,Javier Cortes,Javier Cortes,Jorge S. Reis-Filho,Joan Seoane,Joan Seoane,Joan Seoane +40 more
TLDR
It is shown that ctDNA derived from central nervous system tumours is more abundantly present in the cerebrospinal fluid (CSF) than in plasma, allowing the identification of actionable brain tumour somatic mutations and facilitating and complement the diagnosis of leptomeningeal carcinomatosis.Abstract:
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.read more
Citations
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Integrative Genomics Viewer
James T. Robinson,Helga Thorvaldsdottir,Wendy Winckler,Mitchell Guttman,Eric S. Lander,Eric S. Lander,Gad Getz,Jill P. Mesirov +7 more
TL;DR: The sheer volume and scope of data posed by this flood of data pose a significant challenge to the development of efficient and intuitive visualization tools able to scale to very large data sets and to flexibly integrate multiple data types, including clinical data.
Journal ArticleDOI
Liquid biopsies come of age: towards implementation of circulating tumour DNA
Jonathan C. M. Wan,Charles E. Massie,Javier Garcia-Corbacho,Florent Mouliere,James D. Brenton,Carlos Caldas,Simon Pacey,Richard D. Baird,Nitzan Rosenfeld +8 more
TL;DR: The field is now in an exciting transitional period in which ctDNA analysis is beginning to be applied clinically, although there is still much to learn about the biology of cell-free DNA.
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Integrating liquid biopsies into the management of cancer
TL;DR: How different forms of liquid biopsies can be exploited to guide patient care and should ultimately be integrated into clinical practice is examined, focusing on liquid biopsy of ctDNA — arguably the most clinically advanced approach.
Journal ArticleDOI
Integrated digital error suppression for improved detection of circulating tumor DNA
Aaron M. Newman,Alexander F. Lovejoy,Daniel M. Klass,David M. Kurtz,Jacob J. Chabon,Florian Scherer,Henning Stehr,Chih Long Liu,Scott V. Bratman,Carmen Say,Li Zhou,Justin N. Carter,Robert B. West,George W. Sledge,Joseph B. Shrager,Billy W. Loo,Joel W. Neal,Heather A. Wakelee,Maximilian Diehn,Ash A. Alizadeh +19 more
TL;DR: This work introduces an approach for integrated digital error suppression (iDES), which combines in silico elimination of highly stereotypical background artifacts with a molecular barcoding strategy for the efficient recovery of cfDNA molecules, and facilitates noninvasive variant detection across hundreds of kilobases of circulating tumor DNA.
Journal ArticleDOI
Current and future perspectives of liquid biopsies in genomics-driven oncology.
TL;DR: The potential of liquid biopsies is highlighted by studies that show they can track the evolutionary dynamics and heterogeneity of tumours and can detect very early emergence of therapy resistance, residual disease and recurrence, but their analytical validity and clinical utility must be rigorously demonstrated before this potential can be realized.
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TL;DR: An analysis tool for the detection of somatic mutations and copy number alterations in exome data from tumor-normal pairs is presented and new light is shed on the landscape of genetic alterations in ovarian cancer.
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