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 Previous Article | Table of Contents | Next Article 
Blood, Vol. 94 No. 9 (November 1), 1999:
pp. 3114-3120
Clinicopathogenetic Significance of Chromosomal Abnormalities in
Patients With Blastic Peripheral B-Cell Lymphoma
By
Brigitte Schlegelberger,
Thomas Zwingers,
Lana Harder,
Hadwiga Nowotny,
Reiner Siebert,
Michael Vesely,
Heinrich Bartels,
Ruth Sonnen,
Georg Hopfinger,
Alexander Nader,
German Ott,
Konrad Müller-Hermelink,
Alfred Feller, and
Renate Heinz for the
Kiel-Wien-Lymphoma Study Group
From the Department of Human Genetics, University of Kiel; Estimate
GmbH, Augsburg; Germany; Ludwig-Boltzmann Institute for Leukemia
Research and Hematology, Third Medical Department and the Department of
Pathology, Hanusch Hospital, Vienna, Austria; Jakob Erdheim Institute
for Pathology and Clinical Bacteriology, Lainz Hospital, Vienna,
Austria; Municipal Hospital, Lübeck, Germany; Hospital St Georg,
Hamburg, Germany; the Department of Pathology, Hanusch Hospital,
Vienna, Austria; the Department of Pathology, University of
Würzburg, Germany; and the Department of Pathology, Medical
University of Lübeck, Germany.
 |
ABSTRACT |
So far, reproducible histomorphologic and immunological criteria to
distinguish clinicopathologic subtypes of blastic peripheral B-cell
non-Hodgkin's lymphoma (BBCL), especially centroblastic (cb) and
immunoblastic (ib) lymphomas, for daily diagnostic use are still
lacking. Therefore, we correlated the cytogenetic findings in 126 patients with BBCL with histopathologic diagnoses. Subclassification of
cb and ib lymphomas relied on the criteria defined in the updated Kiel
classification; these subtypes are also listed in the Revised European-American Lymphoma (REAL) classification and in a
preliminary report on the newly established World Health
Organization classification, to investigate their clinical
significance. Moreover, we performed a multivariate analysis to compare
the prognostic significance of cytogenetic findings with the
International Index. There were significant differences in the
frequency of chromosome aberrations between different BBCL subtypes:
t(8;14) was predominantly present in Burkitt's lymphomas, t(14;18) in
centroblastic lymphomas, deletions in 8q and 14q, changes of 4q and
losses of chromosome 10 in immunoblastic lymphomas; t(11;14) was
restricted to blastoid mantle cell lymphomas and associated with a poor
prognosis. In cb lymphomas, deletions in 1q42-qter, duplications in
1q23-32, trisomy 5, and changes of 15q were identified as independent
prognostic factors. In ib lymphomas, changes of 7q and 8q had stronger
impact on survival than the International Index. These findings
underline that Burkitt's, cb, ib, and blastoid mantle-cell lymphoma
are biologically distinct and clinically relevant entities and that
cytogenetic findings can be helpful to subtype BBCL.
© 1999 by The American Society of Hematology.
| |
INTRODUCTION |
MOST CLASSIFICATION systems of
non-Hodgkin's lymphomas (NHL) are based on histological,
cytomorphological, and immunological criteria. It has been a long
debate whether these criteria alone may be sufficient to reproducibly
define clinicopathologic entities. In the Kiel classification,
different subtypes of blastic B-cell lymphomas (BBCL), mainly
centroblastic (cb) and immunoblastic (ib), are distinguished according
to their cytomorphologic and immunohistochemic appearance.1
As indicated by the results of a prospective, randomized, multicenter
trial, the survival of patients with these morphologically defined
entities differs significantly.2 Many hematopathologists
are not accustomed to using the Kiel classification, because, the
Working Formulation predominating the Americal pathology practice in
the past, the Kiel classification was only widely applied
by European hematopathologists, whereas nowadays, the proposal of the
International Lymphoma Study Group3 is generally accepted
as the standard lymphoma classification system. This proposal questions
the possibility to distinguish certain subtypes of large B-cell
lymphomas, especially cb and ib lymphomas, based on morphological or
cytomorphological criteria resulting in lumping a number of different
subtypes as "diffuse large B-cell lymphoma" in the REAL
classification. A preliminary report on the newly established WHO
classification of NHL,4 for which a final publication is
pending, suggested to list these morphologic variants of large B-cell
lymphomas to test their clinical significance. Because typical
cytogenetic changes of NHL, eg, the translocations t(8;14)(q24;q32) in
Burkitt's lymphomas (BL),5 t(14;18)(q32;q21) in follicular
lymphomas,6 t(11;14)(q13;q32) in mantle cell
lymphomas,7 or t(3;14)(q27;q32) in diffuse large cell
lymphomas8 are associated with distinct clinicopathologic entities of NHL, it may be useful to integrate cytogenetic criteria in
the definition of biologically relevant subtypes of NHL, which may
differ in their biological behavior and, thus, may require different
treatment strategies. All these translocations affecting the
immunoglobulin heavy chain (IgH) locus in 14q32 lead to upregulation of
oncogenes located at the chromosomal breakpoints of the translocation partners like c-myc in case of t(8;14),9 bcl-2 in case of
t(14;18),10 CCND1 (bcl-1) in case of
t(11;14),11 or bcl-6 in case of t(3;14).12 Albeit all these translocations can be detected by polymerase chain reaction (PCR) or Southern blot analysis, chromosome analysis has
been shown to be still more reliable at the time of diagnosis than
these molecular methods.13 Certainly, molecular methods are
reliable tools for the analysis of genetic aberrations with a sensitivity comparable with karyotyping for most applications, and
even more reliable for selected investigations. In the present study,
we investigated whether histomorphologic subtypes of BBCL can be
distinguished according to the presence of distinct chromosomal abnormalities and whether cytogenetic findings are independent prognostic factors.
| |
MATERIALS AND METHODS |
One hundred twenty-six patients with blastic B-cell lymphomas
consecutively referred to the Department of Human Genetics, University
of Kiel, Germany, and to the Ludwig-Boltzmann Institute for Leukemia
Research, Vienna, Austria, for cytogenetic analyses were included in
this study, given that analyzable metaphases were found. The clinical
characteristics of the patients are shown in Table
1. Median observation time from primary
diagnosis of a BBCL was 21 months (range, 1 to 112 months). Chromosome
analyses were part of the diagnostic process at the time of the first
diagnosis.
Parts of the same lymph node biopsies (n = 114), bone marrow
(n = 8), spleen (n = 2), pleural effusion (n = 1), and tumor tissue from prostate (n = 1) were used both for chromosome analyses and for histopathological diagnoses. Giemsa- and
hematoxylin-eosin-stained sections were carefully evaluated, and
immunhistochemical staining against CD19, CD20, CD22,  -,  -light
chain restriction, CD30, and CD3 was additionally applied if necessary.
In a few selected cases, monoclonal proliferation of B cells was
confirmed by clonal rearrangements of the CDR III IgH locus.
Subclassification of BBCL relied on the criteria defined in the updated
Kiel classification1 and in the REAL
classification.3 In particular, within diffuse large cell
lymphomas, cb lymphomas were diagnosed if more than 10% of the cells
resembled centroblasts and if the tumor cells were multilobulated or
admixed with up to 90% immunoblasts or other cells; ib lymphomas were
diagnosed if more than 90% of the cells resembled immunoblasts. A
centroblast was regarded as a medium-sized to large cell, with a rim of
slightly to moderately basophilic cytoplasm, and round to oval nuclei
with vesicular chromatin and peripheral nucleoli, or as a like cell
with a multilobulated nucleus. An immunoblast was defined as a large
cell with broad basophilic cytoplasm and a round vesicular nucleus with
a solitary central nucleolus. For a detailed description of the
different subtypes of BBCL, refer to Lennert and Feller.1
One hundred twenty-six cases of this study comprised 96 diffuse large
cell lymphomas according to the REAL classification, which were
subtyped into 68 cb lymphomas, 28 B-ib lymphomas according to the Kiel classification, 11 BL, 11 blastoid mantle cell lymphoma (bMCL, which is
a subtype previously termed centrocytoid centroblastic lymphoma and
recently recognized as blastoid MCL14) and 8 unclassified BBCL. The selection and classification criteria were entirely based on
the Kiel classification.
Chromosome analyses were performed according to standard methods on
unstimulated short-term cultures and cultures stimulated by B-
and T-cell growth supplement or calcium ionophore A 23187 and
phorbol-12,13-dibutyrate as described.15,16 If possible, at
least 20 metaphases were analyzed after fluorescence R/C banding using
chromomycin A3, methyl green, or
4,6-Diamidino-2-phenylindole (DAPI) as fluorescence dyes.
Description of the karyotypes followed the rules of the International
System for Human Cytogenetic Nomenclature (ISCN).17 The cytogenetic findings of 43 cases
have been published previously.16,18,19 Patients underwent
routine diagnostic procedures and were classified according to
the Ann Arbor system. Clinical data and risk profiles according to the
International Prognostic Index20 for patients with
different morphological subtypes of BBCL are shown in Table 1.
With the exception of 2 patients of advanced age, all patients were
treated with anthracyclin-containing chemotherapy (CHOP, CHOEP,
COP-BLAM, PROMACE, CytaBOM).21 Eleven patients received high-dose chemotherapy with stem cell support or autologous bone marrow
transplantation. In a multivariate analysis, we found no differences in
survival between different therapeutic modalities used.
To evaluate survival probabilities and to define the prognostic
significance of various chromosome aberrations, patients with cb and ib
subtypes were analyzed separately. Survival times were estimated by
Kaplan-Meier and compared by Log-Rank test. Cox proportional hazard
model was used to investigate the influence of multiple risk factors
simultaneously. Frequencies of certain chromosome abnormalities in
defined subtapes of BBCL were compared and analyzed by the exact Fisher
test. Statistical significance was defined as P < .05. No
adjustment of the error probabilities for multiple testing was
performed because of the explorative nature of the study.
| |
RESULTS |
Cytogenetic findings.
Aberrant clones were detected in 116 of 126 BBCL studied; complex
aberrant clones containing 4 or more abnormalities were found in 88 of
the 126 BBCL studied (Table 2). BL were
found to have complex aberrant clones significantly less frequent than the other BBCL (P = .001). Hypodiploid chromosome numbers
were found in 6 cb, 7 ib, 2 BL, 6 bMCL, and 1 other BBCL; pseudodiploid chromosome numbers were found in 16 cb, 5 ib, 4 BL, 3 bMCL, and 2 other
BBCL; hyperdiploid chromosome numbers were found in 31 cb, 10 ib, 3 BL,
1 bMCL, and 1 other BBCL; near-triploid chromosome numbers in 2 cb;
near-tetraploid chromosome numbers in 8 cb, 4 ib, 1 BL, 1 bMCL, and in
2 other BBCL. Unidentifiable marker chromosomes were present in 27 cb,
9 ib, 3 BL, 1 bMCL, and in 4 BBCL.
Comparing numerical and structural abnormalities in cb and ib
lymphomas, which were the 2 largest groups of this series, gains of
chromosomes X, 3, 5, 7, 12, and 18 and losses of chromosomes Y, 6, 13, 15, and 17 were the most frequent numerical aberrations in cb lymphomas
(Fig 1); gains of chromosomes 3, 7, 12, and
18 and losses of chromosomes Y, 8, 10, 14, and 21 were most frequent in
ib lymphomas (Fig 2). The series of BL and
bMCL were too small for a detailed analysis. Recurrent
breakpoints were localized in the following regions: 1cen-p13, 1p34-36,
1q42-43, 3q21-22, 3q27-29, 6q12-16, 6q23, 6q25, 8cen-p12, 8q24,
9cen-p21, 12cen-p12, 14q32, 17cen-p11, 18q21, 19p13, and 19q13 in cb
lymphomas (Fig 3); and in 1cen, 2q32, 7q34,
8q21, 8q24, 9q32, 14q32, 15cen, 16p12, 18cen, 18q21, 19p13, and 22q12
in ib lymphomas (Fig 4). Commonly gained
chromosomal regions were: 1q23-31, 3q21-22, 6p, 7p, 7q31-32, 8q22-24,
11q12-13, 12q14-24, and 18q11-21 in cb lymphomas (Fig 5); 1q21-25, 3p24-q21, 6p21, 7p12-21, 18q,
and 22q12-ter in ib lymphomas (Fig 6).
Commonly deleted chromosomal regions were: 1p35-ter, 2p23-ter, 6q21-22,
6q25-ter, 8p12-ter, 9p21-ter, 11q23-ter, 12p12-13, and 17p12-13 in cb
lymphomas (Fig 5); 1p35-36, 2q22-24, 4q32-ter, 6q21-25, 7q33, 8q21,
9p24, 9q21-32, 11q21-ter, 14q23-ter, 16p13, and 18q21-ter in ib
lymphomas (Fig 6).
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| Fig 1.
Numerical chromosome aberrations in cb lymphomas
(n = 68). +, gain;  , loss of the respective chromosome.
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| Fig 2.
Numerical chromosome aberrations in B-ib lymphomas
(n = 28). +, gain; , loss of the respective chromosome.
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| Fig 5.
Chromosomal imbalances in cb lymphomas (n = 68). Each
bar indicates the gain (right side) or loss (left side) of the
respective chromosomal region in 1 lymphoma case.
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| Fig 6.
Chromosomal imbalances in B-ib lymphomas (n = 28).
Each bar indicates the gain (right side) or loss (left side) of the
respective chromosomal region in 1 lymphoma case.
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Presence of chromosomal abnormalities in different subtypes of BBCL.
The groups of patients with morphologically defined subgroups of BBCL,
ie, BL, cb, ib, bMCL subtypes were compared with regard to the
frequency of chromosomal abnormalities. It turned out that t(8;14) was
present most frequently in BL, t(14;18) in cb lymphomas, and t(11;14)
in bMCL, whereas translocations involving 3q27 were seen in different
subtypes of BBCL in similar frequencies (Table 2).
The typical Burkitt's translocation t(8;14) was present in 6 of 11 BL
and in 2 of 68 cb lymphomas, but not in any case of ib lymphoma. No
variant translocations, t(2;8)(p13;q24) or t(8;22)(q24;q11), were seen.
The differences between BL and cb lymphoma as well as between BL and ib
lymphoma regarding the frequency of t(8;14) are highly significant
(P < .0001 for both tests). Structural aberrations
involving 8q24 other than t(8;14), eg, dup(8)(q22q24) or
t(4;8)(q33;q24), were found in 1 case of BL, in 5 cases of cb, in 5 cases of ib, and in 1 case of bMCL subtypes. In 1 case of BL, in 4 cases of cb, and in 1 case of ib subtype, these changes of 8q24
occurred in addition to t(14;18) and in 1 case of bMCL in addition to
t(11;14)(q13;q32). Thus, changes of 8q24 in these cases seem to
represent secondary changes. t(14;18) was present in 2 of 11 BL, in 20 of 68 cb, and in 1 of 28 ib lymphomas. The difference between cb and ib
subtypes with respect to the frequency of t(14;18) is highly
significant (P = .006). t(11;14) was detected only in all 11 bMCL. There was no significant difference between these subtypes of
BBCL regarding the frequency of t(3;14) or changes of 3q27.
When other chromosomal abnormalities were compared for their frequency
in the 2 largest groups, ie, cb and ib subtypes, losses of the whole
chromosome 10, deletions in 8q and 14q, as well as structural
abnormalities of 4q, were significantly more frequent in ib than in cb
lymphomas (P = .01 for 10; P = .017 for
del(8)(q); P = .009 for del(14)(q); P = .049 for der(4)(q).
Survival.
Median survival was 68.9 months for the patients with cb lymphoma, 16.3 months for the patients with ib lymphoma, 38.7 months for patients with
BL, 14.4 months for patients with bMCL, and 15.2 months for patients
with unclassified BBCL, which is in agreement with the results of a
prospective, randomized, multicenter therapy trial that showed that the
distinction of cb and ib lymphomas is a significant prognostic risk
factor.2 As in this study, the difference between our
patients with cb lymphoma and patients with ib lymphoma was
statistically significant (P = .004).
Prognostic significance of chromosomal abnormalities in different
subtypes of BBCL.
The prognostic significance of cytogenetic findings was separately
analyzed for patients with cb and B-ib lymphoma. The presence or
absence of t(8;14), or other changes of 8q24, of t(14;18), and of
t(3;14), or other changes of 3q27 did not influence the survival
probability. However, as shown in Fig 7,
patients with t(11;14)-positive bMCL had a significant shorter survival
than the patients with cb lymphoma, 2 subtypes that, based on
morphologic appearance, can sometimes hardly be distinguished
(P = .003). Other chromosome abnormalities associated with a
significantly shorter survival are given in Table
3. In multivariate testing performed to
evaluate a possible relationship between cytogenetic findings and
established prognostic risk factors of the International Index,
deletions and duplications of 1q were independent adverse risk factors,
whereas trisomy 5 and changes of 15q were independent favorable risk
factors in patients with cb subtypes. In ib subtypes, changes of 7q and
8q had a stronger impact on survival than the International Prognostic
Index (Table 4).
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| Fig 7.
Overall survival of 68 patients with cb lymphomas
compared to 11 patients with t(11;14)-positive lymphomas. This
translocation was only present in the blastic variant of mantle cell
lymphomas previously termed anaplastic mantle cell lymphoma or
centrocytoid cb lymphoma.
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Table 3.
Chromosomal Abnormalities as Adverse Risk Factors
for Survival in 68 Patients With cb and 28 Patients With B-ib
Lymphoma (Univariate Analysis, Log-Rank test)
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Table 4.
Clinical Parameters of the International Index and
Chromosomal Abnormalities as Risk Factors for Survival in 68 Patients With cb and 28 Patients With B-ib Lymphoma (Multivariate
Analyses)
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| |
DISCUSSION |
Cytogenetic findings may help to recognize biologically relevant
entities that are sometimes hard to distinguish by morphologic, cytomorphologic, and immunologic criteria alone.22 This
distinction is especially important if patients with defined entities
run a distinct clinical course as has been shown by Engelhard et
al2 for patients with cb and ib lymphomas, 2 BBCL subtypes
of similar morphological appearance originally described in the Kiel
classification.1 They were able to show in a prospective,
randomized, multicenter trial that the distinction between cb and ib
lymphomas is a significant prognostic risk factor. These results were
confirmed in our study. The patients with cb and ib lymphomas had about
the same survival times as in the study by Engelhard et
al,2 although they were not homogenously treated. However,
except for 2 patients, all of them had received anthracyclin-containing
regimes. In line with a study comparing a standard
anthracyclin-containing regime (CHOP) with intensified
protocols,21 patients treated with different therapy
modalities did not have any differences in survival. Thus, the
diagnosis of an ib lymphoma seems to be an independent adverse risk
factor. Nevertheless, there is an ongoing discussion as to whether
diffuse large cell B-cell lymphomas as defined in the REAL
classification should be subclassified into cb and ib lymphomas.
The presence of typical chromosome abnormalities in morphologically
defined entities of BBCL seems, for the first time, to provide evidence
that ib lymphomas are a distinct biological entity. As to the frequency
of t(8;14), there was a significant difference between ib lymphomas and
BL. This appears to be important, because based on morphology, it is
often difficult to distinguish ib lymphomas with plasmocytic
differentiation from Burkitt-like lymphomas. Moreover, we found
significant differences in the frequency of translocations t(14;18)
between ib and cb lymphomas, and in the frequency of t(11;14) between
ib lymphomas and bMCL. Thus, translocations involving the IgH locus at
14q32 occur less frequently in ib lymphomas than in the other BBCL
studied. These karyotypic findings are confirmed by fluorescence in
situ hybridization (FISH) analyses using a C /VH assay to detect
break events in the IgH locus (R.S., T. Springer, B.S.,
unpublished data, March 1999). Comparably, in small cell B-cell
lymphomas, chronic lymphocytic leukemias (CLLs) (small
lymphocytic lymphomas) only rarely have translocations involving the
IgH locus in 14q32 (H. Doehner, personal communication, November
1998), in contrast to other low grade B-cell lymphomas, eg, centrocytic cb lymphomas (follicular lymphomas grade 1 or 2)23 with t(14;18), mantle-cell lymphomas with t(11;14)
or plasmocytomas.24 Moreover, deletions in 14q, a recurrent
abnormality of ib subtypes in this study, seem to be a characteristic
finding in diffuse B-lymphocytic lymphomas25 and in
CLL.26 In this cytogenetic study, characteristic chromosome
aberrations of CLL, ie, del(11)(q21-q22), +12, del(13)(q14-21), were
present more frequently in ib than in cb lymphomas. However, these
differences were not statistically significant. Trisomy 12 may be only
regarded, if it is present as primary change, meaning, if it does not
occur as a secondary abnormality in addition to t(14;18) or t(8;14).
Within this series, there was 1 ib lymphoma with trisomy 12 as single
change. Because FISH has a higher sensitivity than karyotyping to
detect trisomies and chromosomal deletions, FISH seems to be the method
of choice to clarify whether chromosome aberrations characteristic of
B-CLL indeed occur more frequently in ib than in cb lymphomas and
whether some ib lymphomas may represent the blastic counterpart of
CLL. This hypothesis would be in accordance with the fact
that cases of CLL repeatedly transformed into ib
lymphomas.1
One of 28 ib lymphomas in this study and 7 of 153 ib lymphomas reported
in Mitelman's catalogue of chromosome aberrations27 in
cancer, 104 of them diagnosed according to the Working Formulation, had
a t(14;18). Remarkably, the ib lymphoma of this study and 3 ib
lymphomas reported by Mitelman27 additionally showed a Burkitt's translocation or other structural changes of 8q24. In these
cases, changes of 8q24 may appear as secondary changes during the
karyotypic evolution.28 Recently, amplifications of the chromosomal region 8q24, resulting in an overexpression of the c-myc
gene, were identified by comparative genomic hybridization in
follicular lymphomas with a large cell component that often habor a
t(14;18).29 Patients with both t(14;18) and t(8;14) or
t(8;22) often present in a leukemic phase and run an extremely aggressive course.30 Thus, lymphomas with both t(14;18) and alterations of 8q24 may be a unique clinicopathologic entity.
So far no characteristic chromosome abnormalities of ib lymphomas have
been identified.31 Schouten et al32 assumed
that patients with an abnormal chromosome 6 had an increased frequency to suffer from ib lymphoma.29 In this study, there was no
significant difference between cb and ib lymphomas with respect to
deletions in 6q. However, deletions in 6q turned out to have prognostic significance for patients with ib lymphomas. Offit et al33
and Bastard et al34 described bcl-6 or LAZ3 rearrangements,
the molecular counterpart of t(3;14) or other changes of 3q27, in patients with different subtypes of BBCL, among them follicular and ib
lymphomas. In line with these findings t(3;14)(q27;q32) or other
changes of 3q27 were not associated with a certain subtype of BBCL in
this study. In contrast, loss of chromosome 10, deletions in 8q and
14q, as well as structural abnormalities of 4q, were found
significantly more frequent in ib than in cb lymphomas. In a study of
78 previously untreated patients with NHL, monosomy 14 was the only
abnormality associated with a statistically significant difference in
survival duration.35 When analyzing 104 patients with
diffuse large cell lymphomas from a cytogenetic study of 434 consecutively ascertained specimens, breaks at 1q21-23 and the presence
of more than 4 marker chromosomes were associated with a shortened
median survival.8 Deletions of 1q and duplications of 1q
were also identified in our survival analysis as independent cytogenetic risk factors for patients with cb subtypes. These findings
appear contradictory; detailed analyses of the cytogenetic data,
however, shows that the deletions involve the terminal region 1q42  qter, the duplications involve the region 1q23-32. Moreover, we found a
significant, but favorable, impact on survival of trisomy 5 and changes
of 15q. In the multivariate analysis on patients with ib subtypes,
changes of 7q and 8q even had more impact on survival than the
parameter of the International Index.20 Remarkably, the
recently cloned gene for Nijmegen breakage syndrome, a chromosomal instability syndrome with an increased predisposition for lymphomas, especially of ib subtype, has been localized to 8q21.36
Possibly, mutations of this gene play a role for the development of
B-ib lymphomas, as has been shown for mutations of the related
ataxia-telangiectasia gene in patients with T-PLL.37
The t(11;14) was exclusively present in bMCL, an entity previously
termed centrocytoid centroblastic lymphoma and recently recognized to
represent the blastic counterpart of mantle-cell lymphomas.14 bMCL subtypes were characterized by elevated
mitotic counts, proliferation indices, frequent bcl-1 rearrangements at the major translocation cluster locus, overexpression of p53, and
tetraploid chromosome numbers. Weisenburger and Armitage38 reported patients with diffuse MCL to have a significantly shorter survival of 30 to 33 months when compared to those with a nodular pattern who had a median survival of 77 to 88 months. In the present study, t(11;14) turned out to be an adverse prognostic factor. Thus,
BBCL with t(11;14) seem to be a distinct histomorphologic entity
associated with a remarkably poor outcome.
Recently, FISH assays for the detection of the typical translocations
t(8;14), t(11;14), t(14;18), and t(3;14) have been developed. At the
time of primary diagnosis, their sensitivity exceeded that of
chromosome analysis and even that of molecular techniques like PCR or
Southern blotting.13,19 Studies are underway using these highly sensitive FISH techniques to approve our findings that different
clinicopathologic entities of BBCL can be distinguished based on the
significantly different frequencies of typical chromosome translocations.
| |
FOOTNOTES |
The cytogeneticists H. Grüner (Wien), A. Borowski, K. Rohde, the
pathologists Dr Hanak (Wien), Dr Merz (Lübeck), Prof Dr Parwaresch (Kiel), and clinicians from different hospitals in Germany,
in particular Dr Kuse (Hamburg), Prof Dr Löffler, Prof Dr Schmitz
(Kiel), Dr K. Hoffmann, and B. Liedtke also contributed to this work.
Submitted December 21, 1998; accepted June 28, 1999.
Supported by the Deutsche Krebshilfe, Grant No. 10-0992-Schl3, the
Interdisciplinary Center for Clinical Cancer Research, University
Hospital Kiel, and the Wilhelm Sander-Stiftung Grant No. 95.003.2. B.S.
holds a Hermann und Lilly Schilling professorship.
The publication costs of this
article were defrayed in part by
page charge payment. This article
must therefore be hereby marked
"advertisement"
in accordance with 18 U.S.C. section
1734 solely to indicate this fact.
Address reprint requests to Brigitte Schlegelberger, MD,
Department of Human Genetics, University of Kiel, Schwanenweg 24, 24105 Kiel, Germany; e-mail: schlegelberger{at}medgen.uni-kiel.de.
| |
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TOP
ABSTRACT
INTRODUCTION
, 5 breakpoints; 