Cell-Free DNA from Ascites and Pleural Effusions: Molecular Insights into Genomic Aberrations and Disease Biology

Abstract

Collection of cell-free DNA (cfDNA) from the blood of individuals with cancer has permitted noninvasive tumor genome analysis. Detection and characterization of cfDNA in ascites and pleural effusions have not yet been reported. Herein, we analyzed cfDNA in the ascites and pleural effusions from six individuals with metastatic cancer. In all cases, cfDNA copy number variations (CNV) were discovered within the effusate. One individual had a relevant alteration with a high copy amplification in EGFR in a never smoker with lung cancer, who showed only MDM2 and CDK4 amplification in a prior tissue biopsy. Another subject with metastatic breast cancer had cytology-positive ascites and an activating PIK3CA mutation identified in the tissue, blood, and ascites collectively. This individual had tumor regression after the administration of the mTOR inhibitor everolimus and had evidence of chromotripsis from chromosomal rearrangements noted in the cell-free ascitic fluid. These results indicate that cfDNA from ascites and pleural effusions may provide additional information not detected with tumor and plasma cell-free DNA molecular characterization, and a context for important insights into tumor biology and clonal dynamic change within primary tumor and metastatic deposits. Mol Cancer Ther; 16(5); 948-55. Ó2017 AACR.

Liquid biopsy in breast cancer: A comprehensive review

“…This preference is due to the fact that the serum usually contains extensive amounts of background germline DNA lysed during clotting . In breast cancer cases, plasma is the main fluid sample used for ctDNA analysis, while other bodily fluids are utilized for other cancer types . For example, cerebrospinal fluid (CSF) is a valuable reservoir of ctDNA in tumors of the central nervous system (CNS), because the blood–brain barrier prevents intravasation of ctDNA out of CSF .…”

“…Similarly, transrenal DNA (trDNA) could be used in cancers of the urogenital tract . Other bodily fluids, such as saliva, pleural effusions and even feces, are used for different types of cancer as a complementary approach to blood biopsy . In addition, while plasma is the primary fluid sample used in breast cancer, other bodily fluids can be utilized for metastatic breast cancer depending on the location of metastasis.…”

“…[90][91][92][93] In breast cancer cases, plasma is the main fluid sample used for ctDNA analysis, while other bodily fluids are utilized for other cancer types. 94,95 For example, cerebrospinal fluid (CSF) is a valuable reservoir of ctDNA in tumors of the central nervous system (CNS), because the blood-brain barrier prevents intravasation of ctDNA out of CSF. 96,97 Similarly, transrenal DNA (trDNA) could be used in cancers of the urogenital tract.…”

“…94 Other bodily fluids, such as saliva, pleural effusions and even feces, are used for different types of cancer as a complementary approach to blood biopsy. 95,98,99 In addition, while plasma is the pri-…”

Detection of EGFR gene mutation status from pleural effusions and other body fluid specimens in patients with lung adenocarcinoma

“…Therefore, determining the original EGFR mutation status and monitoring the changes in mutations is crucial to the management of NSCLC, but biopsies are invasive procedures and can be technically impossible in some patients. So far, the concept of liquid biopsy has expanded from blood‐based resources to urine, saliva, effusion, cerebrospinal fluid and other body fluid, which acts as a simple, fast and cost efficient alternative for monitoring of disease status, or response to treatment in multiple malignancies, including lung cancer . A milestone is the approval for Cobas EGFR Mutation Test v2 (cobas, Roche Diagnostic US, Indianapolis, IN, USA) by the United States Food and Drug Administration (US FDA) in 2016.…”