High-resolution genomic screening in mantle cell lymphoma--specific changes correlate with genomic complexity, the proliferation signature and survival.
Mantle cell lymphoma (MCL) is characterized by the t(11;14)(q13;q32) and numerous copy number aberrations (CNAs). Recently, gene expression profiling defined a proliferation gene expression signature in MCL where high scores predict shorter survival. We investigated 31 MCL cases using high-density single nucleotide polymorphism arrays and correlated CNA patterns with the proliferation signature and with clinical data. Many recurrent CNAs typical of MCL were detected, including losses at 1p (55%), 8p (29%), 9q (29%), 11q (55%), 13q (42%) and 17p (32%), and gains at 3q (39%), 8q (26%), 15q (23%) and 18q (23%). A novel deleted region at 20q (16%) contained only one candidate gene, ZFP64, a putative tumor suppressor. Unsupervised clustering identified subgroups with different patterns of CNAs, including a subset (19%) characterized by the presence of 11q loss in all cases and by the absence of 13q loss, and 3q and 7p gains. Losses at 1p, 8p, 13q and 17p were associated with increased genomic complexity. High proliferation signature scores correlated with increased number of large (>15 Mbp) CNAs (P = 0.03) as well as copy number gains at 7p (P = 0.02) and losses at 9q (P = 0.04). Furthermore, large/complex 13q losses were associated with improved survival (P < 0.05) as were losses/copy number neutral LOH at 19p13 (P = 0.01). In summary, this high-resolution genomic analysis identified novel aberrations and revealed that several CNAs correlated with genomic complexity, the proliferation status and survival.
Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden. anna.margret.halldorsdottir@klinimm.uu.se
Anna M
AM
Halldórsdóttir
Birgitta
B
Sander
Hanna
H
Göransson
Anders
A
Isaksson
Eva
E
Kimby
Mahmoud
M
Mansouri
Richard
R
Rosenquist
Hans
H
Ehrencrona
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D002872:Chromosome Deletion; D016000:Cluster Analysis; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005820:Genetic Testing; D006801:Humans; D053208:Kaplan-Meier Estimate; D019656:Loss of Heterozygosity; D020522:Lymphoma, Mantle-Cell / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D017384:Sequence Deletion
D014408:Biomarkers, Tumor