Genome-wide profiling of follicular lymphoma by array comparative genomic hybridization reveals prognostically significant DNA copy number imbalances.
The secondary genetic events associated with follicular lymphoma (FL) progression are not well defined. We applied genome-wide BAC array comparative genomic hybridization to 106 diagnostic biopsies of FL to characterize regional genomic imbalances. Using an analytical approach that defined regions of copy number change as intersections between visual annotations and a Hidden Markov model-based algorithm, we identified 71 regional alterations that were recurrent in at least 10% of cases. These ranged in size from approximately 200 kb to 44 Mb, affecting chromosomes 1, 5, 6, 7, 8, 10, 12, 17, 18, 19, and 22. We also demonstrated by cluster analysis that 46.2% of the 106 cases could be sub-grouped based on the presence of +1q, +6p/6q-, +7, or +18. Survival analysis showed that 21 of the 71 regions correlated significantly with inferior overall survival (OS). Of these 21 regions, 16 were independent predictors of OS using a multivariate Cox model that included the international prognostic index (IPI) score. Two of these 16 regions (1p36.22-p36.33 and 6q21-q24.3) were also predictors of transformation risk and independent of IPI. These prognostic features may be useful to identify high-risk patients as candidates for risk-adapted therapies.
Cheung
K-John J
KJ
Center for Lymphoid Cancer, British Columbia Cancer Agency, 600 West 10th Avenue, Vancouver, BC, Canada.
Shah
Sohrab P
SP
Steidl
Christian
C
Johnson
Nathalie
N
Relander
Thomas
T
Telenius
Adele
A
Lai
Betty
B
Murphy
Kevin P
KP
Lam
Wan
W
Al-Tourah
Abdulwahab J
AJ
Connors
Joseph M
JM
Ng
Raymond T
RT
Gascoyne
Randy D
RD
Horsman
Douglas E
DE
D000465:Algorithms; D001706:Biopsy; D055028:Comparative Genomic Hybridization; D005260:Female; D018628:Gene Dosage; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008224:Lymphoma, Follicular / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008390:Markov Chains; D008875:Middle Aged; D008957:Models, Genetic; D011237:Predictive Value of Tests; D011379:Prognosis; D012307:Risk Factors; D016019:Survival Analysis