Microarray-based genomic profiling reveals novel genomic aberrations in follicular lymphoma which associate with patient survival and gene expression status.
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 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: -1p36 (18%), +2p15 (24%), -3q (14%), -6q (25%), +7p (19%), +7q (23%), +8q (14%), -9p (16%), -11q (15%), +12q (20%), -13q (11%), -17p (16%), +18p (18%), and +18q (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 -6q25 and -6q26, an association with inferior survival was observed.
Schwaenen
Carsten
C
Abt Innere Medizin III, Zentrum für Innere Medizin der Universität Ulm, Ulm, Germany. c.schwaenen@klinikum-esslingen.de
Viardot
Andreas
A
Berger
Hilmar
H
Barth
Thomas F E
TF
Bentink
Stefan
S
Döhner
Hartmut
H
Enz
Martina
M
Feller
Alfred C
AC
Hansmann
Martin-Leo
ML
Hummel
Michael
M
Kestler
Hans A
HA
Klapper
Wolfram
W
Kreuz
Markus
M
Lenze
Dido
D
Loeffler
Markus
M
Möller
Peter
P
Müller-Hermelink
Hans-Konrad
HK
Ott
German
G
Rosolowski
Maciej
M
Rosenwald
Andreas
A
Ruf
Sandra
S
Siebert
Reiner
R
Spang
Rainer
R
Stein
Harald
H
Truemper
Lorenz
L
Lichter
Peter
P
Bentz
Martin
M
Wessendorf
Swen
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D002648:Child; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008224:Lymphoma, Follicular / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D055815:Young Adult