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High-resolution genomic screening in mantle cell lymphoma--specific changes correlate with genomic complexity, the proliferation signature and survival.

Halldórsdóttir, Anna M.; Sander, Birgitta; Göransson, Hanna; Isaksson, Anders; Kimby, Eva; Mansouri, Mahmoud; Rosenquist, Richard and Ehrencrona, Hans LU (2011) In Genes, Chromosomes and Cancer 50(2). p.113-121
Abstract
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... (More)
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. (Less)
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author
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Loss of Heterozygosity, Kaplan-Meier Estimate, Humans, Genetic Testing, Neoplastic, Gene Expression Regulation, Gene Expression Profiling, Female, DNA Copy Number Variations, Cluster Analysis, Chromosome Deletion, 80 and over, Adult, Aged, Lymphoma, Mantle-Cell, Male, Middle Aged, Prognosis, Sequence Deletion, Tumor Markers, Biological
in
Genes, Chromosomes and Cancer
volume
50
issue
2
pages
113 - 121
publisher
John Wiley & Sons
external identifiers
  • scopus:78649982904
ISSN
1045-2257
language
English
LU publication?
no
id
45f0b9ad-c155-43c4-ba03-c08434a70f45 (old id 4020847)
alternative location
http://dx.doi.org/10.1002/gcc.20836
http://www.ncbi.nlm.nih.gov/pubmed/21117067
date added to LUP
2013-10-21 11:00:45
date last changed
2017-10-22 04:56:10
@article{45f0b9ad-c155-43c4-ba03-c08434a70f45,
  abstract     = {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 (&gt;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 &lt; 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.},
  author       = {Halldórsdóttir, Anna M. and Sander, Birgitta and Göransson, Hanna and Isaksson, Anders and Kimby, Eva and Mansouri, Mahmoud and Rosenquist, Richard and Ehrencrona, Hans},
  issn         = {1045-2257},
  keyword      = {Loss of Heterozygosity,Kaplan-Meier Estimate,Humans,Genetic Testing,Neoplastic,Gene Expression Regulation,Gene Expression Profiling,Female,DNA Copy Number Variations,Cluster Analysis,Chromosome Deletion,80 and over,Adult,Aged,Lymphoma,Mantle-Cell,Male,Middle Aged,Prognosis,Sequence Deletion,Tumor Markers,Biological},
  language     = {eng},
  number       = {2},
  pages        = {113--121},
  publisher    = {John Wiley & Sons},
  series       = {Genes, Chromosomes and Cancer},
  title        = {High-resolution genomic screening in mantle cell lymphoma--specific changes correlate with genomic complexity, the proliferation signature and survival.},
  volume       = {50},
  year         = {2011},
}