Identification of Familial Hodgkin Lymphoma Predisposing Genes Using Whole Genome Sequencing.
familial Hodgkin lymphoma
genetic predisposition to disease
germline variants
next generation sequencing
predisposing genes
variant prioritization
whole genome sequencing
Journal
Frontiers in bioengineering and biotechnology
ISSN: 2296-4185
Titre abrégé: Front Bioeng Biotechnol
Pays: Switzerland
ID NLM: 101632513
Informations de publication
Date de publication:
2020
2020
Historique:
received:
03
12
2019
accepted:
21
02
2020
entrez:
27
3
2020
pubmed:
27
3
2020
medline:
27
3
2020
Statut:
epublish
Résumé
Hodgkin lymphoma (HL) is a lymphoproliferative malignancy of B-cell origin that accounts for 10% of all lymphomas. Despite evidence suggesting strong familial clustering of HL, there is no clear understanding of the contribution of genes predisposing to HL. In this study, whole genome sequencing (WGS) was performed on 7 affected and 9 unaffected family members from three HL-prone families and variants were prioritized using our Familial Cancer Variant Prioritization Pipeline (FCVPPv2). WGS identified a total of 98,564, 170,550, and 113,654 variants which were reduced by pedigree-based filtering to 18,158, 465, and 26,465 in families I, II, and III, respectively. In addition to variants affecting amino acid sequences, variants in promoters, enhancers, transcription factors binding sites, and microRNA seed sequences were identified from upstream, downstream, 5' and 3' untranslated regions. A panel of 565 cancer predisposing and other cancer-related genes and of 2,383 potential candidate HL genes were also screened in these families to aid further prioritization. Pathway analysis of segregating genes with Combined Annotation Dependent Depletion Tool (CADD) scores >20 was performed using Ingenuity Pathway Analysis software which implicated several candidate genes in pathways involved in B-cell activation and proliferation and in the network of "Cancer, Hematological disease and Immunological Disease." We used the FCVPPv2 for further
Identifiants
pubmed: 32211398
doi: 10.3389/fbioe.2020.00179
pmc: PMC7067901
doi:
Types de publication
Journal Article
Langues
eng
Pagination
179Informations de copyright
Copyright © 2020 Srivastava, Giangiobbe, Kumar, Paramasivam, Dymerska, Behnisch, Witzens-Harig, Lubinski, Hemminki, Försti and Bandapalli.
Références
Bioinformatics. 2009 Jul 15;25(14):1754-60
pubmed: 19451168
Blood. 2011 Jul 21;118(3):493-8
pubmed: 21562039
PLoS Genet. 2013;9(8):e1003709
pubmed: 23990802
Expert Opin Investig Drugs. 2018 Jun;27(6):513-522
pubmed: 29855199
Nucleic Acids Res. 2010 Sep;38(16):e164
pubmed: 20601685
Br J Haematol. 2015 Aug;170(3):428-31
pubmed: 25715982
Genome Res. 2012 Sep;22(9):1790-7
pubmed: 22955989
Genome Res. 2005 Jul;15(7):901-13
pubmed: 15965027
J Cell Commun Signal. 2018 Mar;12(1):143-156
pubmed: 29027626
Nat Genet. 2011 Aug 07;43(9):879-882
pubmed: 21822267
Genome Biol. 2010;11(8):R90
pubmed: 20799968
Nat Commun. 2013;4:2549
pubmed: 24149102
Lancet. 2005 Jun 25-Jul 1;365(9478):2216-24
pubmed: 15978930
Nat Genet. 2013 Feb;45(2):136-44
pubmed: 23263490
Nature. 2007 Jun 14;447(7146):799-816
pubmed: 17571346
Cancer Epidemiol Biomarkers Prev. 2014 Dec;23(12):2737-47
pubmed: 25205514
Genome Res. 2005 Aug;15(8):1034-50
pubmed: 16024819
Nucleic Acids Res. 2012 Jan;40(Database issue):D930-4
pubmed: 22064851
Proc Natl Acad Sci U S A. 2009 Sep 1;106(35):14920-5
pubmed: 19706467
J Clin Oncol. 2017 Dec 10;35(35):3898-3905
pubmed: 28976790
Nat Genet. 2014 Aug;46(8):912-918
pubmed: 25017105
N Engl J Med. 2015 Dec 10;373(24):2336-2346
pubmed: 26580448
Ann Oncol. 2018 Oct 1;29(10):2046-2051
pubmed: 30165555
Nat Genet. 2013 Jul;45(7):804-7
pubmed: 23749188
J Cancer. 2016 Jan 29;7(4):467-76
pubmed: 26918061
Nature. 2016 Aug 17;536(7616):285-91
pubmed: 27535533
Nucleic Acids Res. 2000 Jan 1;28(1):352-5
pubmed: 10592272
Haematologica. 2016 Jul;101(7):853-60
pubmed: 27365461
Int Rev Immunol. 2012 Apr;31(2):119-32
pubmed: 22449073
J Med Genet. 2006 Nov;43(11):863-6
pubmed: 17085682
Bioinformatics. 2011 Nov 1;27(21):2987-93
pubmed: 21903627
Int J Cancer. 2018 Oct 15;143(8):2076-2078
pubmed: 29708584
Nat Rev Clin Oncol. 2010 Sep;7(9):508-19
pubmed: 20700108
Blood. 2015 Oct 22;126(17):1990-5
pubmed: 26311361
Nucleic Acids Res. 2018 Jul 2;46(W1):W109-W113
pubmed: 29757393
Br J Haematol. 2018 May;181(3):372-377
pubmed: 29693246
Biomolecules. 2019 Oct 13;9(10):
pubmed: 31614935
J Hematol Oncol. 2017 Jul 28;10(1):145
pubmed: 28754125
JAMA Dermatol. 2019 May 1;155(5):604-609
pubmed: 30586141
Nat Commun. 2014 Jun 12;5:3856
pubmed: 24920014
Nat Genet. 2014 Mar;46(3):310-5
pubmed: 24487276
J Oncol. 2019 May 2;2019:7079604
pubmed: 31186638
Nature. 2015 Oct 1;526(7571):68-74
pubmed: 26432245
Hum Mutat. 2016 Mar;37(3):235-41
pubmed: 26555599
Sci Rep. 2018 Aug 2;8(1):11635
pubmed: 30072699
Cancer Sci. 2017 Apr;108(4):604-611
pubmed: 28403546
Genome Res. 2010 Jan;20(1):110-21
pubmed: 19858363
Bioinformatics. 2019 Jun 1;35(11):1978-1980
pubmed: 30376034
Nat Rev Cancer. 2009 Jan;9(1):15-27
pubmed: 19078975
Lancet Oncol. 2004 Jan;5(1):19-26
pubmed: 14700605
Elife. 2015 Aug 12;4:
pubmed: 26267216