Prospective detection of mutations in cerebrospinal fluid, pleural effusion, and ascites of advanced cancer patients to guide treatment decisions

Many advanced cases of cancer show central nervous system, pleural, or peritoneal involvement. In this study, we prospectively analyzed if cerebrospinal fluid (CSF), pleural effusion (PE), and/or ascites (ASC) can be used to detect driver mutations and guide treatment decisions. We collected 42 CSF, PE, and ASC samples from advanced non-small-cell lung cancer and melanoma patients. Cell-free DNA (cfDNA) was purified and driver mutations analyzed and quantified by PNA-Q-PCR or next-generation sequencing. All 42 fluid samples were evaluable; clinically relevant mutations were detected in 41 (97.6%). Twenty-three fluids had paired blood samples, 22 were mutation positive in fluid but only 14 in blood, and the abundance of the mutant alleles was significantly higher in fluids. Of the 34 fluids obtained at progression to different therapies, EGFR resistance mutations were detected in nine and ALK acquired mutations in two. The results of testing of CSF, PE, and ASC were used to guide treatm..... READ ARTICLE

Molecular Oncology DOI:10.1002/1878-0261.12574

Authors: Sergio Villatoro, Clara Mayo-de-las-Casas, Núria Jordana-Ariza, Santiago Viteri-Ramírez, Mónica Garzón-Ibañez, Irene Moya-Horno, Beatriz García-Peláez, María González-Cao, Umberto Malapelle, Ariadna Balada-Bel, Alejandro Martínez-Bueno, Raquel Campos, Noemí Reguart, Margarita Majem, Remei Blanco, Ana Blasco, María J. Catalán, Xavier González, Giancarlo Troncone, Niki Karachaliou, Rafael Rosell, Miguel A. Molina-Vila

Case StudyKirk SmithSeptember 17, 2019Ascites, Cell-free DNA, Cerebrospinal fluid, Liquid biopsy, Pleural effusion, Solid tumors, Somatic mutations

Cell-free DNA Comprises an In Vivo Nucleosome Footprint that Informs Its Tissues-Of-Origin

Nucleosome positioning varies between cell types. By deep sequencing cell-free DNA (cfDNA), isolated from circulating blood plasma, we generated maps of genome-wide in vivo nucleosome occupancy and found that short cfDNA fragments harbor footprints of transcription factors. The cfDNA nucleosome occupancies correlate well with the nuclear architecture, gene structure, and expression observed in cells, suggesting that they could inform the cell type of origin. Nucleosome spacing inferred from cfDNA in healthy individuals correlates most strongly with epigenetic features of lymphoid and myeloid cells, consistent with hematopoietic cell death as the normal source of cfDNA. We build on this observation to show how nucleosome footprints can be used to infer cell types contributing to cfDNA in pathological states such as cancer. Since this strategy does not rely on genetic differences to distinguish between contributing tissues, it may enable the noninvasive monitoring of a much broader set o..... READ ARTICLE

Cell DOI:10.1016/j.cell.2015.11.050

Authors: Matthew W. Snyder, Martin Kircher, Andrew J. Hill, Riza M. Daza, Jay Shendure

Review PaperKirk SmithJanuary 1, 2016Cell-free DNA, In Vivo Nucleosome Footprint, Tissues-Of-Origin