title: Exome sequencing reveals germline NPAT mutation as a candidate risk factor for Hodgkin lymphoma.
abstract: A strong clustering of Hodgkin lymphoma in certain families has been long acknowledged. However, the genetic factors in the background of familial Hodgkin lymphoma are largely unknown. We have studied a family of 4 cousins with a rare subtype of the disease, nodular lymphocyte predominant Hodgkin lymphoma. We applied exome sequencing together with genome-wide linkage analysis to this family and identified a truncating germline mutation in nuclear protein, ataxia-telangiectasia locus (NPAT) gene, which segregated in the family. We also studied a large number of samples from other patients with Hodgkin lymphoma, and a germline variation leading to the deletion of serine 724 was found in several cases suggesting an elevated risk for the disease (odds ratio = 4.11; P = .018). NPAT is thus far the first gene implicated in nodular lymphocyte predominant Hodgkin lymphoma predisposition.
authors.affiliation: Department of Medical Genetics, University of Helsinki, Helsinki, Finland.
authors.forename: Silva
authors.initials: S
authors.lastname: Saarinen
authors.forename: Mervi
authors.initials: M
authors.lastname: Aavikko
authors.forename: Kristiina
authors.initials: K
authors.lastname: Aittomäki
authors.forename: Virpi
authors.initials: V
authors.lastname: Launonen
authors.forename: Rainer
authors.initials: R
authors.lastname: Lehtonen
authors.forename: Kaarle
authors.initials: K
authors.lastname: Franssila
authors.forename: Heli J
authors.initials: HJ
authors.lastname: Lehtonen
authors.forename: Eevi
authors.initials: E
authors.lastname: Kaasinen
authors.forename: Peter
authors.initials: P
authors.lastname: Broderick
authors.forename: Jussi
authors.initials: J
authors.lastname: Tarkkanen
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Bain
authors.forename: Frédéric
authors.initials: F
authors.lastname: Bauduer
authors.forename: Ali
authors.initials: A
authors.lastname: Ünal
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Swerdlow
authors.forename: Rosie
authors.initials: R
authors.lastname: Cooke
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Mäkinen
authors.forename: Richard
authors.initials: R
authors.lastname: Houlston
authors.forename: Pia
authors.initials: P
authors.lastname: Vahteristo
authors.forename: Lauri A
authors.initials: LA
authors.lastname: Aaltonen
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D005387:Finland / Q000453:epidemiology; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D018095:Germ-Line Mutation; D006689:Hodgkin Disease / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D008224:Lymphoma, Follicular / Q000453:epidemiology / Q000235:genetics; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D012307:Risk Factors; D055815:Young Adult
chemical_list: D018797:Cell Cycle Proteins; C101693:NPAT protein, human; D009687:Nuclear Proteins