Combined linkage and association analysis of classical Hodgkin lymphoma
Metrics: PDF 573 views | HTML 1014 views | ?
Alastair Lawrie1, Shuo Han1,7, Amit Sud2, Fay Hosking2, Timothee Cezard3, David Turner4, Caroline Clark5, Graeme I. Murray1, Dominic J. Culligan6, Richard S. Houlston2 and Mark A. Vickers1,4
1School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, United Kingdom
2Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK
3The Genepool, University of Edinburgh, Edinburgh, United Kingdom
4Scottish National Blood Transfusion Service, Edinburgh, United Kingdom
5Department of Medical Genetics, Aberdeen Royal Infirmary, Aberdeen, United Kingdom
6Department of Haematology, Aberdeen Royal Infirmary, Aberdeen, United Kingdom
7Current address: Clinical Trials Manager, MD Anderson Cancer Centre Investigational Cancer Therapeutics, Houston, TX, USA
Alastair Lawrie, email: firstname.lastname@example.org
Amit Sud, email: email@example.com
Keywords: genetics; Hodgkin lymphoma; mutation; cancer; lymphoma
Received: July 07, 2017 Accepted: March 01, 2018 Published: April 17, 2018
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.