open access

Vol 52, No 4 (2021)
Review article
Submitted: 2021-07-21
Accepted: 2021-07-21
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Genomic studies of Hodgkin lymphoma using circulating cell-free DNA

Iwona Wlodarska1, Lieselot Buedts1, Peter Vandenberghe1
DOI: 10.5603/AHP.2021.0057
·
Acta Haematol Pol 2021;52(4):300-304.
Affiliations
  1. Center for Human Genetics, Catholic University Leuven, Belgium

open access

Vol 52, No 4 (2021)
REVIEW ARTICLE
Submitted: 2021-07-21
Accepted: 2021-07-21

Abstract

The revolutionary finding of cell free DNA (cfDNA) circulating in the bloodstream had a huge impact on the development of non-invasive prenatal testing (NIPT) (obstetrics) and liquid biopsies (oncology). The latter, combined with the sequencing of tumor DNA-containing cfDNA, have been widely applied in cancer research, demonstrating the potential of these techniques to improve prognostication and guide individualized treatment strategies. During routine NIPT analysis of more than 88,000 pregnant women performed in our institution, 14 abnormal genomic profiles suggestive of maternal tumor have been identified. Interestingly, one patient was further diagnosed with classic Hodgkin lymphoma (cHL), a tumor characterized by a low content (< 2%) of neoplastic cells in tumor mass. To examine whether circulating cfDNA can be informative about genomic imbalances in neoplastic Hodgkin/Reed-Sternberg (HRS) cells, we performed a pilot study of nine prospective cHL cases. This study showed that genomic profiles of cfDNA correspond to the profiles of HRS cells. To get further insights into the genome of cHL, a large study on cfDNA from 177 prospective cHL patients was subsequently established. Based on ultra-low pass sequencing of cfDNA from this cohort, we built a comprehensive catalog of genomic abnormalities, as well as their frequencies and patterns. Besides the known recurrent imbalances, such as gain/amplification of 2p16/REL-BCL11A and 9p24/JAK2-CD274-PDCDLG2, novel recurrent abnormalities were identified in cHL. Altogether, we have provided evidence that cHL is characterized by consistent and recurrent genomic imbalances and we have shown the potential of genomic profiling of cfDNA as a novel and non-invasive tool in the diagnosis and follow up of cHL patients.  

Abstract

The revolutionary finding of cell free DNA (cfDNA) circulating in the bloodstream had a huge impact on the development of non-invasive prenatal testing (NIPT) (obstetrics) and liquid biopsies (oncology). The latter, combined with the sequencing of tumor DNA-containing cfDNA, have been widely applied in cancer research, demonstrating the potential of these techniques to improve prognostication and guide individualized treatment strategies. During routine NIPT analysis of more than 88,000 pregnant women performed in our institution, 14 abnormal genomic profiles suggestive of maternal tumor have been identified. Interestingly, one patient was further diagnosed with classic Hodgkin lymphoma (cHL), a tumor characterized by a low content (< 2%) of neoplastic cells in tumor mass. To examine whether circulating cfDNA can be informative about genomic imbalances in neoplastic Hodgkin/Reed-Sternberg (HRS) cells, we performed a pilot study of nine prospective cHL cases. This study showed that genomic profiles of cfDNA correspond to the profiles of HRS cells. To get further insights into the genome of cHL, a large study on cfDNA from 177 prospective cHL patients was subsequently established. Based on ultra-low pass sequencing of cfDNA from this cohort, we built a comprehensive catalog of genomic abnormalities, as well as their frequencies and patterns. Besides the known recurrent imbalances, such as gain/amplification of 2p16/REL-BCL11A and 9p24/JAK2-CD274-PDCDLG2, novel recurrent abnormalities were identified in cHL. Altogether, we have provided evidence that cHL is characterized by consistent and recurrent genomic imbalances and we have shown the potential of genomic profiling of cfDNA as a novel and non-invasive tool in the diagnosis and follow up of cHL patients.  

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Keywords

circulating cell-free DNA, liquid biopsy, genomic profiling, DNA sequencing, Hodgkin lymphoma

About this article
Title

Genomic studies of Hodgkin lymphoma using circulating cell-free DNA

Journal

Acta Haematologica Polonica

Issue

Vol 52, No 4 (2021)

Article type

Review article

Pages

300-304

DOI

10.5603/AHP.2021.0057

Bibliographic record

Acta Haematol Pol 2021;52(4):300-304.

Keywords

circulating cell-free DNA
liquid biopsy
genomic profiling
DNA sequencing
Hodgkin lymphoma

Authors

Iwona Wlodarska
Lieselot Buedts
Peter Vandenberghe

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