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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1999-7-1
pubmed:abstractText
Mantle cell lymphomas (MCLs) are characterized by 11q13 chromosomal translocations and cyclin D1 overexpression. The secondary genetic and molecular events involved in the progression of these tumors are not well known. In this study, we have analyzed 45 MCLs (32 typical and 13 blastoid variants) by comparative genomic hybridization (CGH). To identify the possible genes included in the abnormal chromosome regions, selected cases were analyzed for P53, P16(INK4a), RB, C-MYC, N-MYC, BCL2, BCL6, CDK4, and BMI-1 gene alterations. The most frequent imbalances detected by CGH were gains of chromosomes 3q (49%), 7p (27%), 8q (22%), 12q (20%), 18q (18%), and 9q34 (16%) and losses of chromosomes 13 (44%), 6q (27%), 1p (24%), 11q14-q23 (22%), 10p14-p15 (18%), 17p (16%), and 9p (16%). High-level DNA amplifications were identified in 11 different regions of the genome, predominantly in 3q27-q29 (13%), 18q23 (9%), and Xq28 (7%). The CGH analysis allowed the identification of regional consensus areas in most of the frequently involved chromosomes. Chromosome gains (P =. 02) and losses (P =.01) and DNA amplifications (P =.015) were significantly higher in blastoid variants. The significant differences between blastoid and typical tumors were gains of 3q, 7p, and 12q, and losses of 17p. CGH losses of 17p correlated with P53 gene deletions and mutations. Similarly, gains of 12q and high-level DNA amplifications of 10p12-p13 were associated with CDK4 and BMI-1 gene amplifications, respectively. One of 2 cases with 8q24 amplification showed C-MYC amplification by Southern blot. Alterations in 2p, 3q, 13, and 18q were not associated with N-MYC, BCL6, RB, or BCL2 alterations, respectively, suggesting that other genes may be the targets of these genetic abnormalities in MCLs. Increased number of gains (0 v 1-4 v >4 gains per case) (P =.002), gains of 3q (P =.02), gains of 12q (P =.03), and losses of 9p (P =. 003) were significantly associated with a shorter survival of the patients. These results indicate that an increased number of chromosome imbalances are associated with blastoid variants of MCLs and may have prognostic significance.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
93
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4365-74
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Increased number of chromosomal imbalances and high-level DNA amplifications in mantle cell lymphoma are associated with blastoid variants.
pubmed:affiliation
Hematopathology Section, Laboratory of Anatomic Pathology, Department of Hematology, Hospital Clínic, Villarroel, 170, 08036-Barcelona, Spain.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't