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Blood.
1999 Jun 15;93(12):4365-74.
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Increased number of chromosomal imbalances and
high-level DNA amplifications in mantle cell
lymphoma are associated with blastoid variants.
Bea S,
Ribas M, Hernandez JM, Bosch F, Pinyol M, Hernandez
L, Garcia JL, Flores T, Gonzalez M, Lopez-Guillermo
A, Piris MA, Cardesa A, Montserrat E, Miro R, Campo
E.
Hematopathology Section, Laboratory of Anatomic
Pathology, Department of Hematology, Hospital
Clinic, Villarroel, 170, 08036-Barcelona, Spain.
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.
PMID: 10361135 [PubMed - indexed for
MEDLINE]