Variants at 6q21 implicate PRDM1 in the etiology of therapy-induced second malignancies after Hodgkin's lymphoma

Timothy Best, Dalin Li, Andrew D. Skol, Tomas Kirchhoff, Sarah A. Jackson, Yutaka Yasui, Smita Bhatia, Louise C. Strong, Susan M. Domchek, Katherine L. Nathanson, Olufunmilayo I. Olopade, R. Stephanie Huang, Thomas M. MacK, David V. Conti, Kenneth Offit, Wendy Cozen, Leslie L. Robison, Kenan Onel

Research output: Contribution to journalArticlepeer-review

149 Scopus citations

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.

Original languageEnglish
Pages (from-to)941-943
Number of pages3
JournalNature Medicine
Volume17
Issue number8
DOIs
StatePublished - Aug 2011
Externally publishedYes

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