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

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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; Ehrencrona, Hans.

In: Genes, Chromosomes and Cancer, Vol. 50, No. 2, 2011, p. 113-121.

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Halldórsdóttir, Anna M. ; Sander, Birgitta ; Göransson, Hanna ; Isaksson, Anders ; Kimby, Eva ; Mansouri, Mahmoud ; Rosenquist, Richard ; Ehrencrona, Hans. / High-resolution genomic screening in mantle cell lymphoma--specific changes correlate with genomic complexity, the proliferation signature and survival. In: Genes, Chromosomes and Cancer. 2011 ; Vol. 50, No. 2. pp. 113-121.

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TY - JOUR

T1 - High-resolution genomic screening in mantle cell lymphoma--specific changes correlate with genomic complexity, the proliferation signature and survival.

AU - Halldórsdóttir, Anna M.

AU - Sander, Birgitta

AU - Göransson, Hanna

AU - Isaksson, Anders

AU - Kimby, Eva

AU - Mansouri, Mahmoud

AU - Rosenquist, Richard

AU - Ehrencrona, Hans

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

KW - Loss of Heterozygosity

KW - Kaplan-Meier Estimate

KW - Humans

KW - Genetic Testing

KW - Neoplastic

KW - Gene Expression Regulation

KW - Gene Expression Profiling

KW - Female

KW - DNA Copy Number Variations

KW - Cluster Analysis

KW - Chromosome Deletion

KW - 80 and over

KW - Adult

KW - Aged

KW - Lymphoma

KW - Mantle-Cell

KW - Male

KW - Middle Aged

KW - Prognosis

KW - Sequence Deletion

KW - Tumor Markers

KW - Biological

M3 - Article

VL - 50

SP - 113

EP - 121

JO - Genes, Chromosomes and Cancer

JF - Genes, Chromosomes and Cancer

SN - 1045-2257

IS - 2

ER -