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Low-Coverage Whole Genome Sequencing of Cell-Free DNA From Immunosuppressed Cancer Patients Enables Tumor Fraction Determination and Reveals Relevant Copy Number Alterations

Authors :
Amira Bouzidi
Karim Labreche
Marine Baron
Marianne Veyri
Jérôme Alexandre Denis
Mehdi Touat
Marc Sanson
Frédéric Davi
Erell Guillerm
Stéphanie Jouannet
Frédéric Charlotte
Franck Bielle
Sylvain Choquet
Pierre-Yves Boëlle
Jacques Cadranel
Véronique Leblond
Brigitte Autran
Jean-Marc Lacorte
Jean-Philippe Spano
Florence Coulet
the IDEATION study group
Ahmed Idbaih
Noureddine Balegroune
Amélie Guihot
Ioannis Theodorou
Agusti Alentorn
Isabelle Brocheriou
Anne-Geneviève
Damien Roos Weil
Alberto Picca
Source :
Frontiers in Cell and Developmental Biology, Vol 9 (2021)
Publication Year :
2021
Publisher :
Frontiers Media S.A., 2021.

Abstract

Cell-free DNA (cfDNA) analysis is a minimally invasive method that can be used to detect genomic abnormalities by directly testing a blood sample. This method is particularly useful for immunosuppressed patients, who are at high risk of complications from tissue biopsy. The cfDNA tumor fraction (TF) varies greatly across cancer type and between patients. Thus, the detection of molecular alterations is highly dependent on the circulating TF. In our study, we aimed to calculate the TF and characterize the copy number aberration (CNA) profile of cfDNA from patients with rare malignancies occurring in immunosuppressed environments or immune-privileged sites. To accomplish this, we recruited 36 patients: 19 patients with non-Hodgkin lymphoma (NHL) who were either human immunodeficiency virus (HIV)-positive or organ transplant recipients, 5 HIV-positive lung cancer patients, and 12 patients with glioma. cfDNA was extracted from the patients’ plasma and sequenced using low-coverage whole genome sequencing (LC-WGS). The cfDNA TF was then calculated using the ichorCNA bioinformatic algorithm, based on the CNA profile. In parallel, we performed whole exome sequencing of patient tumor tissue and cfDNA samples with detectable TFs. We detected a cfDNA TF in 29% of immune-suppressed patients (one patient with lung cancer and six with systemic NHL), with a TF range from 8 to 70%. In these patients, the events detected in the CNA profile of cfDNA are well-known events associated with NHL and lung cancer. Moreover, cfDNA CNA profile correlated with the CNA profile of matched tumor tissue. No tumor-derived cfDNA was detected in the glioma patients. Our study shows that tumor genetic content is detectable in cfDNA from immunosuppressed patients with advanced NHL or lung cancer. LC-WGS is a time- and cost-effective method that can help select an appropriate strategy for performing extensive molecular analysis of cfDNA. This technique also enables characterization of CNAs in cfDNA when sufficient tumor content is available. Hence, this approach can be used to collect useful molecular information that is relevant to patient care.

Details

Language :
English
ISSN :
2296634X
Volume :
9
Database :
Directory of Open Access Journals
Journal :
Frontiers in Cell and Developmental Biology
Publication Type :
Academic Journal
Accession number :
edsdoj.60de3ac6cae402cb2bbc555becfa333
Document Type :
article
Full Text :
https://doi.org/10.3389/fcell.2021.661272