title: Whole-genome integrative analysis reveals expression signatures predicting transformation in follicular lymphoma.
abstract: Transformation of follicular lymphoma (FL) to a more aggressive disease is associated with rapid progression and death. Existing molecular markers for transformation are few and their clinical impact is limited. Here, we report on a whole-genome study of DNA copy numbers and gene expression profiles in serial FL biopsies. We identified 698 genes with high correlation between gene expression and copy number, and the molecular network most enriched for these cis-associated genes. This network includes 14 cis-associated genes directly related to the nuclear factor κB (NF-κB) pathway. For each of these 14 genes, the correlated NF-κB target genes were identified and corresponding expression scores were defined. The scores for 6 of the cis-associated NFκB pathway genes (BTK, IGBP1, IRAK1, ROCK1, TMED7-TICAM2, and TRIM37) were significantly associated with transformation. The results suggest that genes regulating B-cell survival and activation are involved in transformation of FL.
authors.affiliation: Centre for Cancer Biomedicine, Oslo University Hospital, Oslo, Norway;
authors.forename: Marianne
authors.initials: M
authors.lastname: Brodtkorb
authors.forename: Ole Christian
authors.initials: OC
authors.lastname: Lingjærde
authors.forename: Kanutte
authors.initials: K
authors.lastname: Huse
authors.forename: Gunhild
authors.initials: G
authors.lastname: Trøen
authors.forename: Marit
authors.initials: M
authors.lastname: Hystad
authors.forename: Vera I
authors.initials: VI
authors.lastname: Hilden
authors.forename: June H
authors.initials: JH
authors.lastname: Myklebust
authors.forename: Ellen
authors.initials: E
authors.lastname: Leich
authors.forename: Andreas
authors.initials: A
authors.lastname: Rosenwald
authors.forename: Jan
authors.initials: J
authors.lastname: Delabie
authors.forename: Harald
authors.initials: H
authors.lastname: Holte
authors.forename: Erlend B
authors.initials: EB
authors.lastname: Smeland
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D018628:Gene Dosage; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D008224:Lymphoma, Follicular / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D018511:Systems Integration; D059467:Transcriptome