Portada Simposios - Supplements - Haematologica

252 Haematologica (ed. esp.), volumen 85, supl. 2, octubre 2000
Table 1. Chromosome regions involved by balanced and
unbalanced chromosome rearrangements in 131 patients
with MCL*
FREQUENCY (N.º of cases)
Chromosome
Total
region breakpoints loss gain N.º of cases
1p21-31 5 7 12
1p36 2 1 3
3/3q 11 11
3q13-21 5 5
3q27-29 3 3
5 4 4
6q15-23 4 11 15
6q24-27 4 4
7q22-32 3 3
8p11-12 4 4
8p23 4 4
8q12 3 3
9p13-23 3 2 5
9q12-22 1 5 6
10p14-15 6 6
10q22-24 2 4 1 7
11q21-23 3 3 1 7
11 5 5
12q24 3 3
13q14 6 6
13q34 3 3
13 14 14
15q26 4 4
17p 7 2 9
19q13 3 3
20 7 7
21 6 6
22 6 6
X 6 6
Y 8 8
*Data derived for 6 studies published in the literature
(references 16, 28-32).
Additional numerical changes, each present in
15-20% of the cases include + 7; + 8, + X, + 12, + 18.
Trisomy 7 was demonstrated to mark progression of
FCCL from a low grade histology towards high grade
histology 6 .
6q21-23 deletions and 17p deletions were described
in several studies to occur at a 15-30 % incidence
in FCCL. Interstudy variablity as to the frequency
of these anomaly may reflect heterogeneity of patient
population as well as different technical approaches
for detection, molecular cytogenetic methods
being more accurate and sensitive than conventional
cytogenetic analysis 7,8 . Shorter survival and shorter
time to transformation were found to be associated
with these deletions, which maintained their prognostic
predictivity in multivariate analysis in a study 4 .
A large body of literature definitely showed that in
many cases with 17p–, monoallelic p53 gene deletion
occurs along with inactivating mutations of the
remaining allele, with consequent p53 loss of function
and protein stabilization 9 .
Though 9p21deletions were rarely detected by
conventional karyotyping, submicroscopic lesions
affecting the p16-p15 genes were described which
were associated with histologic transformation in
some cases 10 . More recently, attention was drawn to
the occurrence of 1p36 aberrations in low grade follicle
centre cell lymphoma, the frequency and significance
of which are presently unknown. By conventional
karyotyping and FISH some recurrent translocations
were identified, i.e. der(1)t(1;1)(p36;q21);
der(1)t(1;1)(p36;q25) and der(1)t(1;9)(p36;q13).
In addition a number of deletions involving the
1p36 band were detected. These rearrangements never
occurred as the sole anomaly and they were also
found in other histologic subsets of NHL, suggesting
that this region may harbor one or more tumor suppressor
genes the disruption of which may contribute
to lymphomagenesis 11 .
Mantle cell lymphoma
Mantle cell lymphoma (MCL) accounts for 3-9 %
of all non-Hodgkin’s lymphomas (NHL) in western
countries and it represents a distinct clinicopathological
entity, having a poor prognosis. This tumor
display peculiar histologic characteristics and a
CD5/CD19+ phenotype, with CD10– and CD23– 12 .
Virtually all cases of MCL were shown to be associated
with the 11;14 translocation, juxtaposing BCL1
sequences and the immunoglobulin heavy-chain locus
on the derivative 14q + chromosome 13,14 .
A list of recurrent chromosome anomalies in MCL
is presented in table 1.
Besides the 11;14 translocation, aberrations
found in > 5 cases in a literature review include: deletions/translocations
(del/t) 6q spanning a large region
comprised between the bands q15-q23 [15 cases];
–13 [14 cases]; del/t 1p21-31 [12 cases]; + 3q
[11 cases]; del/t 17p [9 cases]; 8p translocations
and del(Y) [8 cases each]; –20 [7 cases]; 13q14 deletion,
del/t 11q22-23, del/t 9q, del(10)(q22q24),
–20, –21, –22 and –X [6 cases]. Recurrent sites of chromosomal
rearrangements present in more than
5 % of the cases in MCL were the following: deletions
at 1p21-31; gains of 3q; structural changes of 8p
clustered at 8p11-12 and 8p23; deletions/translocation
of 11q21-23, –20 and –Y. Though any of these
anomalies cannot be regarded as specific for MCL it
is noteworthy that some of them showed a preferential
association with CD5 + B-cell lymphomas. Indeed,
a review of the Mitelman’s catalogue 15 revealed
that deletion involving the 1p21-31 bands were
not found as recurrent chromosome anomalies in
18 cases of follicle centre cell lymphoma, in 20 cases
of large cell lymphoma and in 57 cases of Burkitt’s
lymphoma, whereas they were found in 5/21
small lymphocytic lymphomas (SLL) and in 3/9 MCL.
Likewise, 11q– (17,41) and 8p anomalies were
reported in several SLL and MCL and they have
only been reported occasionally in other low-grade