The landscape of copy number variations in classical Hodgkin lymphoma: a joint KU Leuven and LYSA study on cell-free DNA.
Journal
Blood advances
ISSN: 2473-9537
Titre abrégé: Blood Adv
Pays: United States
ID NLM: 101698425
Informations de publication
Date de publication:
13 04 2021
13 04 2021
Historique:
received:
28
07
2020
accepted:
02
03
2021
entrez:
12
4
2021
pubmed:
13
4
2021
medline:
1
6
2021
Statut:
ppublish
Résumé
The low abundance of Hodgkin/Reed-Sternberg (HRS) cells in lymph node biopsies in classical Hodgkin lymphoma (cHL) complicates the analysis of somatic genetic alterations in HRS cells. As circulating cell-free DNA (cfDNA) contains circulating tumor DNA (ctDNA) from HRS cells, we prospectively collected cfDNA from 177 patients with newly diagnosed, mostly early-stage cHL in a monocentric study at Leuven, Belgium (n = 59) and the multicentric BREACH study by Lymphoma Study Association (n = 118). To catalog the patterns and frequencies of genomic copy number aberrations (CNAs), cfDNA was sequenced at low coverage (0.26×), and data were analyzed with ichorCNA to yield read depth-based copy number profiles and estimated clonal fractions in cfDNA. At diagnosis, the cfDNA concentration, estimated clonal fraction, and ctDNA concentration were significantly higher in cHL cases than controls. More than 90% of patients exhibited CNAs in cfDNA. The most frequent gains encompassed 2p16 (69%), 5p14 (50%), 12q13 (50%), 9p24 (50%), 5q (44%), 17q (43%), 2q (41%). Losses mostly affected 13q (57%), 6q25-q27 (55%), 4q35 (50%), 11q23 (44%), 8p21 (43%). In addition, we identified loss of 3p13-p26 and of 12q21-q24 and gain of 15q21-q26 as novel recurrent CNAs in cHL. At diagnosis, ctDNA concentration was associated with advanced disease, male sex, extensive nodal disease, elevated erythrocyte sedimentation rate, metabolic tumor volume, and HRS cell burden. CNAs and ctDNA rapidly diminished upon treatment initiation, and persistence of CNAs was associated with increased probability of relapse. This study endorses the development of ctDNA as gateway to the HRS genome and substrate for early disease response evaluation.
Identifiants
pubmed: 33843986
pii: S2473-9529(21)00255-X
doi: 10.1182/bloodadvances.2020003039
pmc: PMC8045498
doi:
Substances chimiques
Cell-Free Nucleic Acids
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1991-2002Informations de copyright
© 2021 by The American Society of Hematology.
Références
Nat Genet. 2012 May 06;44(6):642-50
pubmed: 22561516
Oncologist. 2019 Feb;24(2):219-228
pubmed: 30108156
Blood. 2002 Feb 15;99(4):1474-7
pubmed: 11830502
Blood. 2010 Jul 22;116(3):418-27
pubmed: 20339089
Genes (Basel). 2019 Jan 10;10(1):
pubmed: 30634664
Br J Haematol. 2008 Sep;142(6):916-24
pubmed: 18671701
Blood Adv. 2019 Dec 10;3(23):4065-4080
pubmed: 31816062
N Engl J Med. 1998 Nov 19;339(21):1506-14
pubmed: 9819449
Eur J Haematol. 2018 May;100(5):511-517
pubmed: 29377256
Blood. 2012 Oct 25;120(17):3530-40
pubmed: 22955918
Cancer Immunol Res. 2016 Nov;4(11):910-916
pubmed: 27737878
Oncotarget. 2017 Nov 30;8(67):111386-111395
pubmed: 29340061
Ann Oncol. 2018 Oct 1;29(Suppl 4):iv19-iv29
pubmed: 29796651
Blood. 2014 Mar 27;123(13):2062-5
pubmed: 24497532
Proc Natl Acad Sci U S A. 2005 Nov 8;102(45):16368-73
pubmed: 16258065
Haematologica. 2008 Sep;93(9):1318-26
pubmed: 18641027
Ann Oncol. 2019 Jan 1;30(1):85-95
pubmed: 30371735
Nat Methods. 2019 Jun;16(6):505-507
pubmed: 31110280
Genome Biol. 2011;12(4):R41
pubmed: 21527027
Nat Rev Cancer. 2011 Jun;11(6):426-37
pubmed: 21562580
Nat Commun. 2017 Nov 6;8(1):1324
pubmed: 29109393
Genes Chromosomes Cancer. 2003 Oct;38(2):126-36
pubmed: 12939740
Genes Chromosomes Cancer. 2016 May;55(5):428-41
pubmed: 26850007
Blood. 2018 Apr 12;131(15):1654-1665
pubmed: 29500175
Blood. 2018 May 31;131(22):2454-2465
pubmed: 29650799
Onco Targets Ther. 2018 Aug 08;11:4673-4683
pubmed: 30122958
Future Sci OA. 2018 Feb 23;4(4):FSO295
pubmed: 29682327
Cancer Res. 2003 May 15;63(10):2606-9
pubmed: 12750286
Blood. 2010 Oct 28;116(17):3268-77
pubmed: 20628145
Ann Oncol. 2009 Aug;20(8):1408-13
pubmed: 19465421
Lancet Haematol. 2015 Feb;2(2):e55-65
pubmed: 26687610
Blood. 2016 Jun 23;127(25):3127-32
pubmed: 27081097
Leuk Lymphoma. 2019 Feb;60(2):498-502
pubmed: 30068243
Lab Invest. 2018 Nov;98(11):1487-1499
pubmed: 30087457
J Pathol. 2010 Jul;221(3):248-63
pubmed: 20527019
Mediterr J Hematol Infect Dis. 2014 Jul 05;6(1):e2014053
pubmed: 25045461
Blood. 1995 Aug 15;86(4):1464-8
pubmed: 7632954
Oncogene. 2004 Feb 12;23(6):1326-31
pubmed: 14961078
Clin Cancer Res. 2018 Sep 15;24(18):4437-4443
pubmed: 29567812
BMC Cancer. 2012 Oct 05;12:457
pubmed: 23039325
Clin Cancer Res. 2011 May 15;17(10):3443-54
pubmed: 21385932
Blood. 2018 May 31;131(22):2413-2425
pubmed: 29449275
Blood. 2002 Feb 15;99(4):1381-7
pubmed: 11830490
Blood. 2015 Feb 12;125(7):1061-72
pubmed: 25488972
Oncogene. 2002 May 2;21(19):3095-102
pubmed: 12082542
Sci Transl Med. 2012 Nov 28;4(162):162ra154
pubmed: 23197571
Nat Genet. 2012 May 06;44(6):651-8
pubmed: 22561519
Br J Haematol. 2001 Mar;112(3):768-75
pubmed: 11260082
J Clin Invest. 2012 Oct;122(10):3439-47
pubmed: 23023715
J Clin Oncol. 2018 Apr 1;36(10):942-950
pubmed: 29394125
J Clin Oncol. 2016 Aug 10;34(23):2690-7
pubmed: 27069084
Eur J Nucl Med Mol Imaging. 2014 Jun;41(6):1113-22
pubmed: 24570094
Leukemia. 2020 Jan;34(1):151-166
pubmed: 31431735
Nat Med. 2014 Apr;20(4):430-5
pubmed: 24658074
N Engl J Med. 2015 Jan 22;372(4):311-9
pubmed: 25482239
J Clin Oncol. 2018 Oct 1;36(28):2845-2853
pubmed: 30125215
Haematologica. 2016 Sep;101(9):1094-101
pubmed: 27479820