% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Srivastava:154585,
      author       = {A. Srivastava$^*$ and S. Giangiobbe$^*$ and A. Kumar$^*$
                      and N. Paramasivam$^*$ and D. Dymerska and W. Behnisch and
                      M. Witzens-Harig and J. Lubinski and K. Hemminki$^*$ and A.
                      Försti$^*$ and O. R. Bandapalli$^*$},
      title        = {{I}dentification of {F}amilial {H}odgkin {L}ymphoma
                      {P}redisposing {G}enes {U}sing {W}hole {G}enome
                      {S}equencing.},
      journal      = {Frontiers in Bioengineering and Biotechnology},
      volume       = {8},
      issn         = {2296-4185},
      address      = {Lausanne},
      publisher    = {Frontiers Media},
      reportid     = {DKFZ-2020-00864},
      pages        = {179},
      year         = {2020},
      note         = {#EA:B062#EA:C050##LA:C050#LA:B062#},
      abstract     = {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 in silico analyses and prioritized
                      45 coding and 79 non-coding variants from the three
                      families. Further literature-based analysis allowed us to
                      constrict this list to one rare germline variant each in
                      families I and II and two in family III. Functional studies
                      were conducted on the candidate from family I in a previous
                      study, resulting in the identification and functional
                      validation of a novel heterozygous missense variant in the
                      tumor suppressor gene DICER1 as potential HL predisposition
                      factor. We aim to identify the individual genes responsible
                      for predisposition in the remaining two families and will
                      functionally validate these in further studies.},
      cin          = {C050 / B062 / HD01 / C020},
      ddc          = {570},
      cid          = {I:(DE-He78)C050-20160331 / I:(DE-He78)B062-20160331 /
                      I:(DE-He78)HD01-20160331 / I:(DE-He78)C020-20160331},
      pnm          = {312 - Functional and structural genomics (POF3-312)},
      pid          = {G:(DE-HGF)POF3-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:32211398},
      pmc          = {pmc:PMC7067901},
      doi          = {10.3389/fbioe.2020.00179},
      url          = {https://inrepo02.dkfz.de/record/154585},
}