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Blood, Vol. 93 No. 12 (June 15), 1999:
pp. 4365-4374
Increased Number of Chromosomal Imbalances and High-Level DNA
Amplifications in Mantle Cell Lymphoma Are Associated With Blastoid
Variants
Sílvia Beà,
Maria Ribas,
Jesús M. Hernández,
Francesc Bosch,
Magda Pinyol,
Luis Hernández,
Juan Luis García,
Teresa Flores,
Marcos González,
Armando López-Guillermo,
Miguel A. Piris,
Antonio Cardesa,
Emilio Montserrat,
Rosa Miró, and
Elías Campo
From the Hematopathology Section, Laboratory of Anatomic Pathology,
and Department of Hematology, Hospital Clínic, Institut
d'Investigacions Biomèdiques "August Pi i Sunyer"
(IDIBAPS), University of Barcelona, Barcelona, Spain; the Department of
Cellular Biology and Physiology, Autonomous University of Barcelona,
Barcelona, Spain; the Laboratory of Anatomic Pathology, Hospital Virgen
de la Salud, Toledo, Spain; and the Department of Hematology, Hospital
Clínico, Universidad de Salamanca, Salamanca, 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,
P16INK4a, 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.
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