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 Previous Article | Table of Contents | Next Article 
Blood, Vol. 91 No. 1 (January 1), 1998:
pp. 231-237
Molecular Delineation of 13q Deletion Boundaries in 20 Patients
With Myeloid Malignancies
By
R. La Starza,
I. Wlodarska,
A. Aventin,
D. Falzetti,
B. Crescenzi,
M.F. Martelli,
H. Van den Berghe, and
C. Mecucci
From the Hematology Unit, University of Perugia, Perugia, Italy;
Center for Human Genetics and Flanders Interuniversity Institute of
Biotechnology, University of Leuven, Leuven, Belgium; and the
Department of Hematology, University Hospital San Pau, Barcelona,
Spain.
 |
ABSTRACT |
Fluorescent in situ hybridization (FISH) analysis with
a panel of DNA probes for 13q13.1-q14.3 was performed on 20 cases of
myeloid malignancies, of which 17 showed a del(13)(q) and three had
translocations affecting 13q. By chromosome morphology, deletions
consistently involved bands q14 and q21. In addition to confirming the
chromosome data, FISH allowed us to delineate a commonly deleted region
that was flanked by YAC 833A2 and YAC 854D4. Three cases with 13q
translocations unexpectedly showed accompanying cryptic microdeletions
of 13q, and in one case the commonly deleted region could be narrowed
to a genomic segment, which includes YAC 937C7, RB1, and YAC 745E3.
Homozygous deletions were not detected. This region overlaps with the
smallest deleted region of 13q14 in chronic lymphocytic leukemia.
| |
INTRODUCTION |
CHROMOSOMAL deletions are among the most
common genetic events observed in solid tumors and hematologic
malignancies. Loss of genetic material in neoplastic cells is
suggestive of a recessive mechanism in the pathogenesis of these
disorders and is regarded as a hallmark of putative tumor suppressor
gene(s) localization. In myeloid disorders, the most frequently
reported deletions affect chromosomes 5, 7, and 20.1
Deletions of chromosomes 11, 12, and 13 are less frequent, but
recurrent.1 Loss of chromosome 13q material is mainly
observed in myeloproliferative disorders (MPD), but it also occurs in
myelodysplastic syndromes (MDS) and acute myeloid leukemia
(AML).2 In most cases the deletions have been described as
interstitial and only in a few cases as terminal.2 Attempts
to correlate the extent of the deletions with the type of myeloid
malignancy have been made and loss of 13q12-q32 bands appeared to be
prevalent in MPD, 13q12-q22 in MDS, and the 13q21 band in
AML.1 It is noteworthy that one of the well-known tumor
suppressor genes, the retinoblastoma gene (RB1), has been assigned to
13q14.3
Recently, some molecular studies on the status of this gene in myeloid
malignancies have been published. Ahuja et al4 detected RB1
involvement in rearrangements or intragenic deletions in 5 of 54 cases
of AML and in 2 of 18 cases of MDS. In another series of 69 AML cases,
RB1 gene rearrangements were not found by Southern blot
analysis.5 Similarly, gene rearrangements could not be
detected in studies on AML cases in which a significant lack of RB1
protein expression was found.6,7 Also, in a series of 90
cases of MDS, the RB1 gene configuration proved to be
germline.8 Finally, in 1 case of AML and one case of
agnogenic myeloid metaplasia (AMM), both with a del(13)(q) determined
at cytogenetic level, Morris et al9 found heterozygous
deletions of the RB1 gene.
Interestingly, rearrangements of chromosome 13, at bands q13-q21,
account for 12% of structural changes in chronic lymphocytic leukemia
(CLL) with abnormal karyotypes10 and were found in larger
numbers of cases when molecular investigations were
performed.11,12 The RB1 gene was shown to be deleted in
20% of CLL analyzed by fluorescent in situ hybridization
(FISH)11 and in 30% of cases investigated by quantitative
Southern blot analysis.12 Homozygous deletions of RB1,
however, have been sporadically detected.11 Recently, Brown
et al13 reported CLL cases in which RB1 was not lost and
drew attention to the D13S25 locus telomeric to RB1 that was lost in 9
of 10 analyzed cases. Additional studies using the LOH (loss of
heterozygosity) assay,14,15 quantitative Southern
blot,16 and FISH17 strongly suggested that a
putative tumor suppressor gene, implicated in the pathogenesis of CLL,
might be located between the RB1 gene and the D13S25 marker. Bullrich
et al18 restricted the smallest critical region to a
segment of 550 kb between 206XF12 and D13S25 marker at band 13q14.
In contrast with the rapid accumulation of molecular findings on 13q
deletions in lymphoid disorders, molecular data on 13q chromosome
deletions in myeloid malignancies are still scarce, to the extent that
no results from molecular cytogenetics are available so far. We report
here on 20 cases of various myeloid disorders in which we characterized
deletions of 13q by FISH with the aim of determining a commonly deleted
region at the molecular level.
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MATERIALS AND METHODS |
Patients.
Patients with myeloid diseases and deletions or translocations of
chromosome 13 were retrieved from the files of the Center for Human
Genetics in Leuven, Belgium, Hospital Sant Pau in Barcelona, Spain, and
from the Hematology and Bone Marrow Transplantation Unit in Perugia,
Italy. All clinical files of the patients were reviewed. A total of 20
cases were included with the following diagnoses: 6 MDS, 5 AMM, 4 AML,
2 essential thrombocythemia (ET), 1 polycytemia vera (PV), 1
Ph-positive CML, and 1 atypical CML. There were 10 female and 10
male patients. Some data about these patients are shown in Table
1.
Cytogenetics.
Bone marrow and/or peripheral blood cells were cultured for 24
or 48 hours without stimulation. Metaphases were R-banded with acridine
orange or G-banded with Wright stain. Karyotypes were described
according to the International System for Human Cytogenetic
Nomenclature (1995).
FISH studies.
FISH was performed as previously described19 using nine
biotin-16-dUTP labeled YACs selected from reported
STS-based maps.20,21 YACs assigned to the 13q13.1-q14.3
region are ordered as follows:
centromere-951A3-765A10-833A2-875A8-911F6-937C7-745E3-935G2-854D4-telomere
(Table 2). The RB1 gene was investigated
with probe LSI 13/RB1 spectrum orange DNA (Vysis Inc, Downers Grove,
IL). A chromosome 13/21 (pUC 1.76) centromeric probe directly labeled
with fluorescein-5-dUTP or Texas Red-5-dCTP was used for
identifying the der(13) in each case. In some experiments, on case 18,
a centromeric probe for chromosome 12 (pRB-12) was also applied. An
additional two-color painting with a digoxigenin-11-dUTP labeled
library 8, and a biotin-16-dUTP labeled library 13 was performed in
case 20. A median of seven abnormal metaphases (range, 3 to 9) were
studied by FISH and G-banding for each case. The FISH data were
collected on a Leitz fluorescence microscope equipped with a cooled CCD
camera (Photometrics) run by SmartCapture software (Vysis, Stuttgart,
Germany).
| |
RESULTS |
Cytogenetics.
Cytogenetic results are shown in Table 1. In all but 4 cases the 13q
anomaly was found at diagnosis. In 2 cases del(13)(q) appeared during
the course of disease (cases 6 and 16), and the remaining 2 cases (13
and 15) were only studied 2 and 11 years after diagnosis, respectively.
Abnormal metaphases carrying the 13q anomaly ranged from 40% to 100%
of analyzed cells. Seventeen cases were classified as interstitial
deletions with the following breakpoints: q13q21 in 12 cases, q13q22 in
1 case, q14q22 in 2 cases, q12q21 in 2 cases (Fig
1). Based on chromosome morphology, loss of
material at bands 13q14-21 was common to all cases with a del(13)(q).
Deletion of 13q was present either as the sole abnormality (9 cases) or
as part of a complex karyotype (8 cases). In two cases it was
associated with trisomy 8 (cases 11 and 12), in 3 cases with a
del(5)(q) (cases 4, 9, and 11).
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| Fig 1.
Schematic representation of 13q chromosome interstitial
deletions determined by conventional cytogenetics in 17 cases with
myeloid malignancies. Black bars show the extent of deletion in each
case; dotted lines delimitate the commonly lost region.
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Translocations involving chromosome 13 were found in 3 cases in which
additional karyotypic abnormalities, including a del(5)(q), were
observed. Patient 18 investigated at diagnosis, as well as 2 months
later, showed a t(12;13)(p13;q14) translocation in 100% of cells in
both analyses. Subclones carrying two copies of a der(13)t(12;13) in
the presence of a normal 13, or only one der(13)t(12;13) with two
normal chromosomes 13, were also identified in this case. A three-way
translocation, ie, t(2;12;13)(p14;q24;q13) was found in patient 19. The
karyotype of case 20 was characterized by complex chromosomal
rearrangements including a der(7)tas(7;13)(7pterqter13qterq14), a
der(13)t(8;13)(21;q14), and multiple unidentified markers.
FISH studies.
Results of FISH studies showing the presence or absence of
hybridization signals of the applied probes for 13q13.1-q14.3 are
summarized in Table 3. Occurrence of
del(13)(q) was confirmed by FISH in all 17 cases. Analysis of the
deleted regions in these cases allowed for the identification of a
commonly deleted region that was proximally flanked by the YAC 833A2
(cases 1 and 8) and distally by the YAC 854D4 (cases 1, 4, 6, 11, 16,
and 17). This region corresponds to bands q13.3-q14.3 (Table 2) and is
covered by 875A8, 911F6, 937C7, LSI/RB1, 745E3, 935G2. FISH performed
in three cases with translocations involving 13q yielded some
unexpected results. The hybridization pattern of 13q probes in the two
cases with balanced translocations involving 13q is shown in Table 3.
In case 18 with a t(12;13)(p13;q14), breakpoints were flanked by 911F6
proximally and 935G2 distally (Fig 2), but
the 937C7, RB1, and 745E3 probes hybridized only to the normal
chromosome 13. Moreover, both copies of a der(13)t(12;13), present in
one of the subclones in this case showed the same hybridization pattern
with the applied probes. The chromosome 13 breakpoint in the
t(2;12;13)(p14;q24;q13) found in case 19 could not be determined (see
Table 3), but loss of one hybridization signal from all applied YACs
was observed.
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Table 3.
Results of FISH Experiments on 20 Myeloid Malignancies
With Deletions or Translocations of Chromosome
13q
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| Fig 2.
Examples of FISH analysis performed in case 18.
Arrowheads in a and c indicate normal chromosome 21 that cohybridize
with pUC 1.76 probe for the centromere of chromosome 13. Probes
applied: (a) pUC 1.76 (cen 13/21) (red) and 911F6 (green). The picture
shows a metaphase with two copies of normal chromosome 13 and one
der(13): YAC 911F6 hybridizes on both normal 13 and on the der(13); (b)
pBR-12 (cen-12) (green) and RB1 (red). Only one red signal,
corresponding to RB1 gene, is kept on normal 13; (c) pUC 1.76 (red) and
937C7 (green). This metaphase represents the subclone with one normal
13 and two copies of der(13): YAC 937C7 is only mantained on normal 13;
(d) pBR-12 (red) and 935G2 (green) in a metaphase with two copies of
normal 13 and one der(13): YAC935G2 is present in three copies, on the
two normal 13 and on the der(12).
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In case 20, YACs 951A3, 833A2, and 875A8 hybridized to the normal
chromosome 13 and to the two copies of the marker defined as mar1 (Fig
3). The 854D4 probe gave a signal on the
normal chromosome 13 and on the telomeric region of der(7), while
937C7, RB1, and 745E3 probes hybridized only to the normal chromosome
13. These results showed that chromosome 13 was involved in the origin
of mar1 and indicated the occurrence of cryptic deletion of 13q in this
case. Further FISH studies with a chromosome 13/21 centromeric probe
and two-color chromosome painting confirmed the presence of chromosome
13 material on the distal fragment of the der(7), as well as on the
proximal region of the two copies of mar1. Chromosome 8 material was
detected not only in the der(13)t(8;13)(q21;q14), but also in two
copies of the mar1 definitely identified as der(13)t(8;13)(q11;q14)
(Fig 3).
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| Fig 3.
Graphical representation of structural rearrangements
involving chromosome 13 in case 20 and summary of FISH analysis.
Chromosome 7 material is shown in red, chromosome 13 in yellow, and
chromosome 8 in green. Order of the applied YACs is indicated next to
the normal chromosome 13.
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| |
DISCUSSION |
We report results of FISH studies performed on 20 cases of myeloid
disorders characterized by deletions (17 cases) or translocations (3
cases) involving chromosome 13. Hematologic diagnoses in the 17 cases
with deletions were heterogeneous, including AML, MDS, as well as
Ph-positive CML and Ph-negative MPD. Cytogenetic findings were
strikingly overlapping (Fig 1), and previous associations between
specific breakpoints and distinct myeloid disorders were not
confirmed.1 These data suggest that the molecular event(s)
undergoing 13q deletions are common to acute and chronic myeloid
disorders. Whether a del(13)(q) is related to initiation or progression
of myeloid malignancies is unknown. However, the finding of this
abnormality in a subclone characterized by a del(5)(q) (case 9), as
well as during the course of disease (cases 6 and 16), suggests that
loss of 13q material was a secondary event. Cytogenetic results were
confirmed by FISH analysis in the 17 cases with cytogenetically
discernible 13q deletions. The large region extending from band q13.3
to q14.3 and flanked by YAC 833A2 and YAC 854D4 was lost in all cases.
Microdeletions accompanying translocations affecting the long arm of
chromosome 13 found by FISH in three cases (18, 19, and 20) could not
be identified by chromosome analysis alone. Similar cryptic deletions
of chromosome 13 involved in translocations have been reported in
CLL.12,13,17,22 Brown et al13 showed the
absence of the D13S25 marker either in the der(13) or in the der(11)
contained in hybrids derived from CLL cells with a t(11;13)(p13;q14).
Hawthorn et al22 also identified a small region of loss
around the D13S25 marker in hybrids derived from a CLL with t(12;13).
Interestingly, another chromosomal region undergoing deletions in
myeloid malignancies, namely 12p, showed a number of cryptic
microdeletions associated with translocations.23 FISH
studies of these microdeletions may be highly informative in the
molecular mapping of putative tumor suppressor loci. Ours is the first
report on cryptic deletions in myeloid cases with only evidence of
translocations involving 13q by conventional cytogenetics. Moreover, it
appears from present data that loss of 13q material, in addition to
translocation, is a consistent event in myeloid malignancies, as it was
found in all three cases analyzed in this molecular cytogenetic study.
Two cases of this study deserve a comment because of peculiar features.
First, the case of MDS with a t(12;13)(p13;q14) was the most
informative because YAC 937C7, the RB1, and YAC 745E3 were exclusively
deleted. These results allowed us to define the smallest deleted region
common to all cases of this myeloid series to the genomic area
corresponding to YAC 937C7, the RB1 gene, and the YAC 745E3.
Second, case 20 provided us with an interesting observation about
chromosomal mechanisms underlying involvement of putative suppressor
gene(s) in 13q deletions of myeloid malignancies. Despite a partial
polysomy of 13q, due to the presence of unbalanced translocations in
the karyotype (Fig 3), the three probes, which identified the critical
region of loss in all of our myeloid disorders (937C7, LSI/RB1, and
745E3), were maintained only on the normal chromosome 13. Conversely,
all of the other analyzed YACs were present in two (854D4) or three
(951A3, 833A2, and 875A8) copies, being retained in at least one of the
13q markers derived from the unbalanced translocations. Loss of the
region covered by YAC 937C7, LSI/RB1, and YAC 745E3 thus appears to be
a critical event in malignant myeloid cells. This large region includes
the smallest 13q segment lost in CLL, which is limited by RB1 and
D13S25 marker.18
It is a subject of recent controversy if in CLL a proximal region,
namely 13q12.3, may be lost in addition to the more
terminal one.24,25 Whether the same region is also involved
in myeloid disorders remains to be determined. Neverthless, the large
extent of lost material shown in this study suggests that more than one
suppressor gene may be involved in 13q deletions of myeloid
malignancies.
| |
FOOTNOTES |
Submitted June 12, 1997;
accepted August 25, 1997.
Supported in part by "Comitato per la vita Daniele Chianelli,"
Pezugio, Italy; and by BIOMED, BMH1-CT94-1703 from the European
Community.
Address reprint requests to C. Mecucci, MD, PhD, Hematology,
Policlinico Monteluce, via Brunamonti, 06123 Perugia, Italy.
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.
| |
ACKNOWLEDGMENT |
We are thankful to Magda Dehaen and the technicians from the Center for
Human Genetics for their expert technical assistance.
| |
REFERENCES |
1.
Johansson B,
Mertens F,
Mitelman F:
Cytogenetic deletion maps of hematologic neoplasms: Circumstantial evidence for tumor suppressor loci.
Genes Chromosom Cancer
8:205,
1993[Medline]
[Order article via Infotrieve]
2. Mitelman F: Catalog of Chromosome Aberrations in Cancer (ed 5).
New York, NY, Wiley, 1994
3.
Sparkes RS,
Sparkes MC,
Wilson MG,
Towner JW,
Benedict W,
Murphree AL,
Yunis JJ:
Regional assignment of genes for human esterase D and retinoblastoma to chromosome band 13q14.
Science
208:1042,
1980[Abstract/Free Full Text]
4.
Ahuja HG,
Jat PS,
Foti A,
Bar-Eli M,
Cline MJ:
Abnormalities of the retinoblastoma gene in the pathogenesis of acute leukemia.
Blood
78:3259,
1991[Abstract/Free Full Text]
5.
Chen Y-C,
Chen P-J,
Yeh S-H,
Tien H-F,
Wang C-H,
Tang J-L,
Hong R-L:
Deletion of the human retinoblastoma gene in primary leukemias.
Blood
76:2060,
1990[Abstract/Free Full Text]
6.
Tang J-L,
Yeh S-H,
Chen P-J,
Lin M-T,
Tien H-F,
Chen Y-C:
Inactivation of the retinoblastoma gene in acute myelogenous leukemia.
Br J Haematol
82:502,
1992[Medline]
[Order article via Infotrieve]
7. Jamal R, Gale RE, Thomas N Shaun B, Wheatley K, Linch DC: The
retinoblastoma gene (rb1) in acute myeloid leukemia: Analysis of gene
rearrangements, protein expression and comparison of disease outcome.
Br J Haematol 94:342, 1996
8.
Preudhomme C,
Vachee A,
Lepelley P,
Vanrumbeke M,
Zandecki M,
Quesnel B,
Cosson A,
Fenaux P:
Inactivation of the retinoblastoma gene appears to be very uncommon in myelodysplastic syndromes.
Br J Haematol
87:61,
1994[Medline]
[Order article via Infotrieve]
9.
Morris CM,
Cochrane JM,
Benjes SM,
Crossen PE,
Fitzgerald PH:
Molecular definition of interstitial deletions of chromosome 13 in leukemic cells.
Genes Chromosom Cancer
3:455,
1991[Medline]
[Order article via Infotrieve]
10.
Hernandez JM,
Mecucci C,
Criel A,
Meeus P,
Michaux L,
Van Hoof A,
Verhoef G,
Louwagie A,
Scheiff J-M,
Michaux J-L,
Boogaerts M,
Van den Berghe H:
Cytogenetic analysis of B cell chronic lymphoid leukemias classified according to morphologic and immunophenotypic (FAB) criteria.
Leukemia
9:2140,
1995[Medline]
[Order article via Infotrieve]
11.
Döhner H,
Pilz T,
Fischer K,
Cabot G,
Diehl D,
Fink T,
Stilgenbauer S,
Bentz M,
Lichter P:
Molecular cytogenetic analysis of RB-1 deletions in chronic B-cell leukemias.
Leuk Lymphoma
16:97,
1994[Medline]
[Order article via Infotrieve]
12.
Liu Y,
Grandér D,
Söderhäll S,
Juliusson G,
Gahrton G,
Einhorn S:
Retinoblastoma gene deletions in B-cell chronic lymphocytic leukemia.
Genes Chromosom Cancer
4:250,
1992[Medline]
[Order article via Infotrieve]
13.
Brown AG,
Ross FM,
Dunne EM,
Steel CM,
Weir-Thompson EM:
Evidence for a tumour suppressor locus (DBM) in human B-cell neoplasia telomeric to the retinoblastoma gene.
Nat Genet
3:67,
1993[Medline]
[Order article via Infotrieve]
14.
Newcomb EW,
Thomas A,
Selkirk A,
Lee SY,
Potmesil M:
Frequent homozygous deletions of D13S218 on 13q14 in B-cell chronic lymphocytic leukemia independent of disease stage and retinoblastoma gene inactivation.
Cancer Res
55:2044,
1995[Abstract/Free Full Text]
15.
Devilder MC,
François S,
Bosic C,
Moreau A,
Mellerin MP,
Le Paslier D,
Bataille R,
Moisan JP:
Deletion cartography around the D13S25 locus in B cell chronic lymphocytic leukemia and accurate mapping of the involved tumor suppressor gene.
Cancer Res
55:1355,
1995[Abstract/Free Full Text]
16.
Liu Y,
Hermanson M,
Grandér D,
Merup M,
Wu X,
Heyman M,
Rasool O,
Juliusson G,
Gahrton G,
Detlofsson R,
Nikiforova N,
Buys C,
Söderhäll S,
Yankovsky N,
Zabarovsky E,
Einhorn S:
13q deletions in lymphoid malignancies.
Blood
86:1911,
1995[Abstract/Free Full Text]
17.
Stilgenbauer S,
Leupolt E,
Ohl S,
Wei G,
Schröder M,
Fischer K,
Bentz M,
Lichter P,
Döhner H:
Heterogeneity of deletions involving RB-1 and the D13S25 locus in B-cell chronic lymphocytic leukemia revealed by fluorescence in situ hybridization.
Cancer Res
55:3475,
1995[Abstract/Free Full Text]
18.
Bullrich F,
Veronese ML,
Kitada S,
Jurlander J,
Caligiuri MA,
Reed JC,
Croce CM:
Minimal region of loss at 13q14 in B-cell chronic lymphocytic leukemia.
Blood
88:3109,
1996[Abstract/Free Full Text]
19.
Dierlamm J,
Wlodarska I,
Michaux L,
La Starza R,
Zeller W,
Mecucci C,
Van den Berghe H:
Successful use of the same slide for consecutive fluorescence in situ hybridization experiments.
Genes Chromosom Cancer
16:261,
1996[Medline]
[Order article via Infotrieve]
20.
Chumakov IM,
Rigault P,
Le Gall I,
Bellanné-Chantelot C,
Billault A,
Guillou S,
Soularue P,
Guasconi G,
Poullier E,
Gros I,
Belova M,
Sambucy J-L,
Susini L,
Gervy P,
Glibert F,
Beaufils S,
Bui H,
Massart C,
De Tand M-F,
Dukasz F,
Lecoulant S,
Ougen P,
Perrot V,
Saumier M,
Soravito C,
Bahouayila R,
Cohen-Akenine A,
Barillot E,
Bertrand S,
Codani J-J,
Caterina D,
Georges I,
Lacroix B,
Lucotte G,
Sahbatou M,
Schmit C,
Sangouard M,
Tubacher E,
Dib C,
Fauré S,
Fizames C,
Gyapay G,
Millasseau P,
Nguyen S,
Muselet D,
Vignal A,
Morissette J,
Menninger J,
Lieman J,
Desai T,
Banks A,
Bray-Ward P,
Ward D,
Hudson T,
Gerety S,
Foote S,
Stein L,
Page DC,
Lander ES,
Weissenbach J,
Le Paslier D,
Cohen D:
A YAC contig map of the human genome.
Nature
377:175,
1995[Medline]
[Order article via Infotrieve]
21. GDB: Human Genome Database [database online]. Whitehead
Institute for Biomedical Research/MIT Center for Genome Research,
available from Internet: http://www-genome.wi.mit.edu/
22.
Hawthorn LA,
Chapman R,
Oscier D,
Cowell JK:
The consistent 13q14 translocation breakpoint seen in chronic B-cell leukaemia (BCLL) involves deletion of the D13S25 locus which lies distal to the retinoblastoma predisposition gene.
Oncogene
8:1415,
1993[Medline]
[Order article via Infotrieve]
23.
Wlodarska I,
Marynen P,
La Starza R,
Mecucci C,
Van den Berghe H:
The ETV6, CDKN1B and D12S178 loci are involved in a segment commonly deleted in various 12p aberrations in different hematological malignancies.
Cytogenet Cell Genet
72:229,
1996[Medline]
[Order article via Infotrieve]
24.
Garcia-Marco JA,
Caldas C,
Price CM,
Wiedemann LM,
Ashworth A,
Catovsky D:
Frequent somatic deletion of the 13q12.3 locus encompassing BRCA2 in chronic lymphocytic leukemia.
Blood
88:1568,
1996[Abstract/Free Full Text]
25. Panayiotidis P, Ganeshaguru K, Hoffbrand AV, Rowntree C, Jabbar
SAB, Foroni L: Deletion of 13q14.3 and not 13q12 is the most common
genetic abnormality detected in chronic lymphocytic leukemia cells.
Blood 89:734,1997
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|
|
|
G. A. Calin, F. Trapasso, M. Shimizu, C. D. Dumitru, S. Yendamuri, A. K. Godwin, M. Ferracin, G. Bernardi, D. Chatterjee, G. Baldassarre, et al.
Familial Cancer Associated with a Polymorphism in ARLTS1
N. Engl. J. Med.,
April 21, 2005;
352(16):
1667 - 1676.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Hirai
Molecular Mechanisms of Myelodysplastic Syndrome
Jpn. J. Clin. Oncol.,
April 1, 2003;
33(4):
153 - 160.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Leroux, F. Mugneret, M. Callanan, I. Radford-Weiss, N. Dastugue, J. Feuillard, F. Le Mee, G. Plessis, P. Talmant, N. Gachard, et al.
CD4+, CD56+ DC2 acute leukemia is characterized by recurrent clonal chromosomal changes affecting 6 major targets: a study of 21 cases by the Groupe Francais de Cytogenetique Hematologique
Blood,
May 13, 2002;
99(11):
4154 - 4159.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Migliazza, F. Bosch, H. Komatsu, E. Cayanis, S. Martinotti, E. Toniato, E. Guccione, X. Qu, M. Chien, V. V. V. Murty, et al.
Nucleotide sequence, transcription map, and mutation analysis of the 13q14 chromosomal region deleted in B-cell chronic lymphocytic leukemia
Blood,
April 1, 2001;
97(7):
2098 - 2104.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Barosi
Myelofibrosis With Myeloid Metaplasia: Diagnostic Definition and Prognostic Classification for Clinical Studies and Treatment Guidelines
J. Clin. Oncol.,
September 1, 1999;
17(9):
2954 - 2954.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
Abstract
Introduction
Abstract