Microarray‐based genomic profiling reveals novel genomic aberrations in follicular lymphoma which associate with patient survival and gene expression status

Abstract

Follicular lymphoma (FL) is characterized by a large number of chromosomal aberrations. However, their exact genomic extension and involved target genes remain to be determined. For this purpose, we used array-based intermediate-high resolution genomic profiling in combination with Affymetrix TM gene expression analysis. Tumor specimens from 128 FL patients were analyzed for the presence of genomic aberrations and the results were correlated to clinical data sets and mRNA expression levels. In 114 (89%) of the 128 analyzed cases, a total of 688 genomic aberrations (384 gains/amplifications and 304 losses) were detected. Frequent genomic aberrations were: À1p36 (18%), þ2p15 (24%), À3q (14%), À6q (25%), þ7p (19%), þ7q (23%), þ8q (14%), À9p (16%), À11q (15%), þ12q (20%), À13q (11%), À17p (16%), þ18p (18%), and þ18q (28%). Critical segments of these imbalances were delineated to genomic fragments with a minimum size down to 0.2 Mb. By comparison of these with mRNA gene expression data, putative candidate genes were identified. Moreover, we found that deletions affecting the tumor suppressor gene CDKN2A/B on 9p21 were detected in nontransformed FL grade I-II. For this aberration as well as for À6q25 and À6q26, an association with inferior survival was observed.

Characterization of a variant of t(14;18) negative nodal diffuse follicular lymphoma with CD23 expression, 1p36/TNFRSF14 abnormalities, and STAT6 mutations

“…This comprised the detection of other recurrent genomic structural aberrations including the loss of 4q34-q35, gain of 3p, 3q, and 12q, all of which can be seen in conventional follicular lymphoma, [23][24][25][26] but are detected at higher frequencies in nodal marginal zone lymphomas. 27,28 Gains of 2p (four cases with three as focal gains of REL, at higher frequency than observed in follicular lymphoma), 9q, and 11p were also recurrently observed.…”

microRNA 28 controls cell proliferation and is down-regulated in B-cell lymphomas

“…expression in GC-derived lymphomas, we investigated both genetic and epigenetic factors. In FL, deletions affecting the host gene of miR-28 (LPP) have been reported (24). As expression of miR-28 and LPP correlates in normal and malignant B cells ( Fig.…”

Inactivation of the CDKN2A Tumor-Suppressor Gene by Deletion or Methylation Is Common at Diagnosis in Follicular Lymphoma and Associated with Poor Clinical Outcome

“…However, the recent application of technology capable of detecting homozygous deletions or copy-neutral LOH, also called acquired uniparental disomy (aUPD), has uncovered such alterations affecting CDKN2A in a substantial 12% to 20% of nontransformed follicular lymphoma samples (9,(15)(16)(17).…”