title: Variants at 6q21 implicate PRDM1 in the etiology of therapy-induced second malignancies after Hodgkin's lymphoma.
abstract: Survivors of pediatric Hodgkin's lymphoma are at risk for radiation therapy-induced second malignant neoplasms (SMNs). We identified two variants at chromosome 6q21 associated with SMNs in survivors of Hodgkin's lymphoma treated with radiation therapy as children but not as adults. The variants comprise a risk locus associated with decreased basal expression of PRDM1 (encoding PR domain containing 1, with ZNF domain) and impaired induction of the PRDM1 protein after radiation exposure. These data suggest a new gene-exposure interaction that may implicate PRDM1 in the etiology of radiation therapy-induced SMNs.
authors.affiliation: Committee on Cancer Biology, University of Chicago, Chicago, Illinois, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Best
authors.forename: Dalin
authors.initials: D
authors.lastname: Li
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Skol
authors.forename: Tomas
authors.initials: T
authors.lastname: Kirchhoff
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Jackson
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yasui
authors.forename: Smita
authors.initials: S
authors.lastname: Bhatia
authors.forename: Louise C
authors.initials: LC
authors.lastname: Strong
authors.forename: Susan M
authors.initials: SM
authors.lastname: Domchek
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Nathanson
authors.forename: Olufunmilayo I
authors.initials: OI
authors.lastname: Olopade
authors.forename: R Stephanie
authors.initials: RS
authors.lastname: Huang
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Mack
authors.forename: David V
authors.initials: DV
authors.lastname: Conti
authors.forename: Kenneth
authors.initials: K
authors.lastname: Offit
authors.forename: Wendy
authors.initials: W
authors.lastname: Cozen
authors.forename: Leslie L
authors.initials: LL
authors.lastname: Robison
authors.forename: Kenan
authors.initials: K
authors.lastname: Onel
mesh_terms: D000367:Age Factors; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D004307:Dose-Response Relationship, Radiation; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006689:Hodgkin Disease / Q000532:radiotherapy*; D006801:Humans; D009154:Mutation / Q000235:genetics*; D016609:Neoplasms, Second Primary / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D000074462:Positive Regulatory Domain I-Binding Factor 1; D025341:Principal Component Analysis; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D011878:Radiotherapy / Q000009:adverse effects*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D012097:Repressor Proteins; C087042:PRDM1 protein, human; D000074462:Positive Regulatory Domain I-Binding Factor 1