Combined linkage and association analysis of classical Hodgkin lymphoma

Alastair Lawrie*, Shuo Han, Amit Sud, Fay Hosking, Timothee Cezard, David Turner, Caroline Clark, Graeme I. Murray, Dominic J. Culligan, Richard S. Houlston, Mark A. Vickers

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Citation (Scopus)
9 Downloads (Pure)

Abstract

The heritability of classical Hodgkin lymphoma (cHL) has yet to be fully deciphered. We report a family with five members diagnosed with nodular sclerosis cHL. Genetic analysis of the family provided evidence of linkage at chromosomes 2q35-37, 3p14-22 and 21q22, with logarithm of odds score > 2. We excluded the possibility of common genetic variation influencing cHL risk at regions of linkage, by analysing GWAS data from 2,201 cHL cases and 12,460 controls. Whole exome sequencing of affected family members identified the shared missense mutations p.(Arg76Gln) in FAM107A and p.(Thr220Ala) in SLC26A6 at 3p21 as being predicted to impact on protein function. FAM107A expression was shown to be low or absent in lymphoblastoid cell lines and SLC26A6 expression lower in lymphoblastoid cell lines derived from p.(Thr220Ala) mutation carriers. Expression of FAM107A and SLC26A6 was low or absent in Hodgkin Reed-Sternberg (HRS) cell lines and in HRS cells in Hodgkin lymphoma tissue. No sequence variants were detected in KLHDC8B, a gene previously suggested as a cause of familial cHL linked to 3p21. Our findings provide evidence for candidate gene susceptibility to familial cHL.

Original languageEnglish
Pages (from-to)20377-20385
Number of pages9
JournalOncotarget
Volume9
Issue number29
DOIs
Publication statusPublished - 17 Apr 2018

Keywords

  • Cancer
  • Genetics
  • Hodgkin lymphoma
  • Lymphoma
  • Mutation

Fingerprint Dive into the research topics of 'Combined linkage and association analysis of classical Hodgkin lymphoma'. Together they form a unique fingerprint.

  • Cite this

    Lawrie, A., Han, S., Sud, A., Hosking, F., Cezard, T., Turner, D., Clark, C., Murray, G. I., Culligan, D. J., Houlston, R. S., & Vickers, M. A. (2018). Combined linkage and association analysis of classical Hodgkin lymphoma. Oncotarget, 9(29), 20377-20385. https://doi.org/10.18632/oncotarget.24872