Characterization of a highly aberrant plasma cell leukemia karyotype: a case report

We report on a 72-year-old patient with a clinically diagnosed plasmocytoma which developed to a plasma cell leukemia (PCL) with so far unrecorded complex translocations. As GTG-banding was not able to resolve all karyotypic changes, multiplex-fluorescence in situ hybridization (M-FISH) in combination with microdissection based comparative genomic hybridization (micro-CGH) and multicolor banding (MCB) have been done. Using these molecular cytogenetic approaches the karyotype of the PCL case can be described as: 51,XY,-1,-1,+3,+der(5)t(5;11;1)(5pter right curved arrow 5q13-q14::11q24 right curved arrow 11q25::1q12 right curved arrow 1qter),+7 or +der(7)t(7;1)(7qter right curved arrow 7p15::1p31.1 right curved arrow 1pter),+8,+der(9)t(1;9)(1qter right curved arrow 1q12::9q12 right curved arrow 9pter),der(11)t(1;11;1)(1pter right curved arrow 1p31.1::11p15.5 right curved arrow 11q25::1q12 right curved arrow 1qter),-13,der(14)t(X;14)(Xqter right curved arrow Xq21.3::14pter right curved arrow 14qter),+15,+18,der(19)t(9;19)(9qter right curved arrow 9q12::19q11 right curved arrow 19pter),+i(19)(q10). The case shows one of the most complex karyotypic rearrangements ever described in PCL and indicates two additional chromosomal regions which may contain genes of interest for the development of this hematological disorder: loss of 1p10-p31.1 material and gain of Xq21.3-qter.     

A complex translocation event between the two homologues of chromosomes 5 leading to a del(5)(q21q33) as a sole aberration in a case clinically diagnosed as CML: characterization of the aberration by multicolor banding

We report on a patient with a clinically diagnosed Philadelphia negative chronic myelogenous leukemia (CML) with a so far unrecorded complex translocation event between the two homologue chromosomes 5. At the GTG-band level the karyotype was normal, apart from an enlarged chromosome 5 and an extremely shortened second chromosome 5. Both derivative chromosomes 5 consisted exclusively of #5 derived material as proven by 24-color FISH. To characterize the complex aberration in more detail the multicolor banding (MCB) technique using a chromosome 5 specific probe set was applied. Using this DNA-based high resolution banding procedure, the karyotype could be described as 46,XX,del(5)(pterright curved arrow q12::q33right curved arrow qter),ins(5)(pterright curved arrow q15::q12right curved arrow q21::q21right curved arrow qter). In consequence, the aberration leads to a partial deletion of the long arm of chromosome 5: del(5)(q21q33), which would not have been identified using conventional banding techniques or 24-color FISH.     

Genetic and pathologic evolution of early secondary gliosarcoma

Gliosarcoma is a subset of glioblastoma with glial and mesenchymal components. True secondary gliosarcomas (i.e. progressing from lower-grade precursors) in the absence of radiation therapy are very rare. We report the unique case of a 61-year-old male who developed a fibrillary astrocytoma (WHO grade II). In the absence of adjuvant therapy the tumor recurred 3 years later as a gliosarcoma comprising an infiltrating glial component and a curious, early high-grade sarcomatous component surrounding intratumoral vessels. DNA was extracted from formalin fixed paraffin-embedded tissues from the precursor low-grade glioma and from the glioma and sarcomatous components at progression. Samples were hybridized separately to a 300 k Illumina SNP array. IDH1(R132H) mutant protein immunohistochemistry was positive in all tissue components. Alterations identified in all samples included dup(1)(q21q41), del(1)(q41qter), del(2)(q31.1), del(2)(q36.3qter), del(4)(q35.1qter), dup(7)(q22.2q36.3), del(7)(q36.3qter), del(9)(p21.3pter), dup(10)(p13pter), del(10)(q26.13q26.3), dup(17) (q12qter), and copy neutral LOH(20)(p11.23p11.21). The recurrent tumor had additional alterations, including del(3)(p21.31q13.31), del(18)(q21.2qter), and a homozygous del(9)(p21.3)(CDKN2A locus) and the sarcoma component had, in addition, del(4)(p14pter), del(6)(q12qter), del(11)(q24.3qter), and del(16)(p11.2pter). In conclusion, unique copy number alterations were identified during tumor progression from a low-grade glioma to gliosarcoma. A subset of alterations developed specifically in the sarcomatous component.     

Construction of mouse A9 clones containing a single human chromosome (X/autosome translocation) via micro-cell fusion

Cell hybrids between hypoxanthine guanine phosphoribosyl transferase (HGPRT)-deficient mouse cell lines (A9 or RAG) and each of 12 different human fibroblasts (GM cells) containing various X/autosome translocations were formed, selected and isolated. Several human chromosomes including an X/autosome translocation carrying HGPRT locus were found in these hybrid cells. To construct A9 cell clones that contain a single X/autosome translocation, micro-cell fusion was undertaken to transfer these chromosomes from the hybrids to A9 cells. Karyotype analysis revealed that most of the resulting micro-cell hybrids contain, in a background of mouse chromosomes, only the human X/autosome translocations which were present in the GM cells used for cell hybridization. Sublines of A9 cells were established containing the following autosomal segments: 1q23----1qter; 1q12----1pter; 3p12----3pter; 3q21----3qter; 11q13----11qter; 11q13----11pter; 11p11----11qter; 11q23----11pter; 12q24----12pter; 16q24----16pter; 17q11----17pter.     

Construction of Mouse A9 Clones Containing a Single Human Chromosome (X/Autosome Translocation) via Micro-cell Fusion

Cell hybrids between hypoxanthine guanine phosphoribosyl transferase (HGPRT)-deficient mouse cell lines (A9 or RAG) and each of 12 different human flbroblasts (GM cells) containing various X/autosome translocations were formed, selected and isolated. Several human chromosomes including an X/autosome translocation carrying HGPRT locus were found in these hybrid cells. To construct A9 cell clones that contain a single X/autosome translocation, micro-cell fusion was undertaken to transfer these chromosomes from the hybrids to A9 cells. Karyotype analysis revealed that most of the resulting micro-cell hybrids contain, in a background of mouse chromosomes, only the human X/autosome translocations which were present in the GM cells used for cell hybridization. Sublines of A9 cells were established containing the following autosomal segments: 1q23→1qter; 1q12→1pter; 3p12→3pter; 3q21→3qter; 11q13→11qter; 11q13→11pter; 11p11→11qter; 11q23→11pter; 12q24→12pter; 16q24→16pter; 17q11→17pter.     

Seven novel and stable translocations associated with oncogenic gene expression in malignant melanoma

Cytogenetics has not only precipitated the discovery of several oncogenes, but has also led to the molecular classification of numerous malignancies. The correct identification of aberrations in many tumors has, however, been hindered by extensive tumor complexity and the limitations of molecular cytogenetic techniques. In this study, we have investigated five malignant melanoma (MM) cell lines from at least three different passages using high-resolution R-banding and the recently developed methods of comparative genomic hybridization and multicolor or multiplex fluorescence in situ hybridization. We subsequently detected nine consistent translocations, seven of which were novel: dic(1;11)(p10;q14), der(9)t(3;9)(p12;p11), der(4)t(9;4;7)(q33:p15-q23:q21), der(14)t(5;14)(q12;q32), der(9)t(9;22)(p21;q11), der(19)t(19;20)(p13.3;p11), der(10)t(2;12;7;10)(q31:p12-->pter:q11.2-->q31:q21), der(19)t(10;19)(q23;q13), and der(20)t(Y;20)(q11.23;q13.3). Furthermore, using the human HG-U133A GeneChip, positive expression levels of oncogenes or tumor-related genes located at the regions of chromosomal breakpoints were identified, including AKT1, BMI1, CDK6, CTNNB1, E2F1, GPNMB, GPRK7, KBRAS2, LDB2, LIMK1, MAPK1, MEL, MP1, MUC18, NRCAM, PBX3, RAB22A, RAB38, SNK, and STK4, indicating an association between chromosomal breakpoints and altered gene expression. Moreover, we also show that growth of all five cell lines can be significantly reduced by downregulating CDK6 gene expression with small interfering RNA (siRNA). Because the majority of these breakpoints have been reported previously in MM, our results support the idea of common mechanisms in this disease.     

Molecular Cytogenetic Characterization of Drug-resistant Leukemia Cell Lines by Comparative Genomic Hybridization and Fluorescence in situ Hybridization

Resistance to chemotherapeutic drugs is one of the major difficulties encountered during cancer chemotherapy. To detect genomic aberrations underlying the acquired drug resistance, we examined three cultured human myelomonocytic leukemia cell sublines each resistant to adriamycin (ADR), 1-β–1- d -arabinofuranosylcytosine (ara-C), or vincristine (VCR), using comparative genomic hybridization (CGH), fluorescence in situ hybridization (FISH), RT-PCR, and western blot techniques. Chromosomes 7, 10 and 16 most conspicuously showed frequent aberrations among the resistant sublines as compared to the parental KY–821 cell line. In ADR-resistant cells, gains at 7q21, 16p12, 16p13.1–13.3, 16q11.1–q12.1, and losses at 7p22–pter, 7q36–qter, 10p12, 10p11.2–pter, 10q21–q25, 10q26–qter were notable. In ara-C-resistant cells, no remarkable gain or loss on chromosome 7, but losses at 10p14–pter, 10q26–qter and 16p11.2–p11.3 were observed. In VCR-resistant cells, gain at 7q21 and losses at 10p11–p13, 10p15 and 16p11.2–p13.3 were found. FISH identified amplified signals for the MDR–1 gene located at 7q21.1 in ADR-and VCR-but not ara-C-resistant cells, and for the MRP–1 gene located at 16pl3.1 in ADR-resistant cells. These findings were validated at the mRNA and protein levels. Overlapping of the amplified MRP–1 gene with MDR–1 gene may play a critical part in the acquisition of resistance to ADR. Resistance to ara-C excluded MDR–1 gene involvement and highlighted other key genes such as MXR gene. Several other genes putatively involved in the development of drug resistance might lie in other aberrated chromosomal regions.     

t(1;7) in acute myeloblastic leukemia following myelodysplastic syndrome (RAEB-T)

A case is described of myelodysplastic syndrome (MDS) refractory anemia type with an excess of blasts in transformation with early leukemic evolution (AML-M1). All bone marrow cells examined showed an unbalanced translocation t(1;7). The karyotype was 45, xy, -21, -7, + der dic t(1;7) (q12;q21). There are reports in the literature of the translocation t(1;7) (p11;p11), which leads to trisomy of the long arms of chromosome #1 and monosomy of the long arms of chromosome #7. In the case here described the breakpoints of the chromosomes involved in the translocation differ from the classic ones: in this case there is trisomy of the region 1q12----1qter and monosomy of the region 7q21----7qter. Some clinical and cytogenetic considerations are suggested.     

Genome‐wide profiling of chromosomal alterations in renal cell carcinoma using high‐density single nucleotide polymorphism arrays

The identification of genetic aberrations may help understand the mechanisms of tumorigenesis and has important implications in diagnosis, prognosis and treatment. We applied Illumina's 317K high‐density single nucleotide polymorphism (SNP) arrays to profile chromosomal aberrations in clear cell renal cell carcinoma (ccRCC) from 80 patients and analyzed the association of LOH/amplification events with clinicopathological characteristics and telomere length. The most common loss of heterozygosity (LOH) were 3p (69 cases) including 38 whole 3p arm losses, 30 large fragment LOH (spanning 3p21‐36), and 1 interstitial LOH (spanning 3p12‐14, 3p21‐22, 3p24.1‐24.2 and 3p24.3), followed by chromosome losses at 8p12‐pter, 6q23.3‐27, 14q24.1‐qter, 9q32‐qter, 10q22.3‐qter, 9p13.3‐pter, 4q28.3‐qter and 13q12.1‐21.1. We also found several smallest overlapping regions of LOH that contained tumor suppressor genes. One smallest LOH in 8p12 had a size of 0.29 Mb and only contained one gene (NRG1). The most frequent chromosome gains were at 5q (32 cases), including 10 whole 5q amplification, 21 large amplifications encompassing 5q32‐ter and 1 focal amplification in 5q35.3 (0.42 Mb). The other common chromosome gains were 1q25.1‐qter, 7q21.13‐qter, 8q24.12‐qter and whole 7p arm. Significant associations of LOH at 9p, 9q, 14q and 18q were observed with higher nuclear grade. Significant associations with tumor stage were observed for LOH at 14q, 18p and 21q. Finally, we found that tumors with LOH at 2q, 6p, 6q, 9p, 9q and 17p had significantly shorter telomere length than those without LOH. This is the first study to use Illumina's SNP–CGH array that provides a close estimate of the size and frequency of chromosome LOH and amplifications of ccRCC. The identified regions and genes may become diagnostic and prognostic biomarkers as well as potential targets of therapy. © 2009 UICC     

Specific patterns of DNA copy number gains and losses in eight new glioblastoma multiforme cell lines

Eight cell lines newly established from glioblastoma multiforme were examined by comparative genomic hybridization for their patterns of genomic imbalance. The total number of DNA copy number alterations (CNAs) found in the eight cell lines varied between 15 and 24. This characterized the examined cell lines (or the tumors they were derived from) as distinctly progressed in karyotypic evolution. The most frequent CNAs were gains of the entire chromosome 6 or, at least, parts of it, and of 7p22, which were found in all eight cell lines. Other changes present in seven of the eight cell lines were gains of 3q26qter and the entire chromosome 7 and losses of segments on chromosome 4q (e.g., 4q34q35) and of the short arm of chromosome 10. Enh(3q21q25), dim(4q22q33) and dim(4qter), dim(13q22), enh(15q14), and enh(18q22q23) were found in six of the eight cell lines. Several other CNAs [e.g., dim(9p21)] were found in common in five or less of the eight lines. Using a hierarchical cluster analysis, the specific patterns of genomic imbalance allowed various groupings of the examined cell lines. Although a close relation could be confirmed among all examined lines on the basis of shared CNAs, two main groups could be roughly differentiated. Among those there were also more or less closely related subgroups. However, also alterations which were restricted to one single cell line each were found, e.g., dim(1q41qter), dim(2q22qter), enh(4p), dim(5p), dim(4p13pter), dim(8q21qter), enh(9p), dim(9q), dim(11p14pter), enh(12q15q23), enh(13q21), dim(14q21qter), dim(15q21qter), dim(19q), and enh(22q). The comparison of the obtained data on gains and losses of DNA copy numbers in specific chromosomal segments with the data on localization of genes possibly associated with the biology of glioblastoma multiforme additionally shows high conformity but also disparity of the examined cell lines among each other, as well as compared to primary glioblastoma multiforme. Eventually, each of the cell lines could be characterized by its specific pattern of genomic imbalance.     

Chromosomal alterations during lymphatic and liver metastasis formation of colorectal cancer

Comparative genomic hybridization (CGH) was used to screen colorectal carcinomas for chromosomal aberrations that are associated with metastatic phenotype. In total, 63 tumor specimens from 40 patients were investigated, comprising 30 primary tumors, 22 systemic metastases (12 liver, 6 brain, and 4 abdominal wall metastases) and 11 lymph node tumors. Using statistical analysis and histograms to evaluate the chromosomal imbalances, overrepresentations were detected most frequently at 20q11.2-20q13.2, 7q11.1-7q12, 13q11.2-13q14, 16p12, 19p13, 9q34, and 19q13.1-19q13.2. Deletions were prominent at 18q12-18q23, 4q27-4q28, 4p14, 5q21, 1p21-1p22, 21q21, 6q16-6q21, 3p12, 8p22-8p23, 9p21, 11q22, and 14q13-14q21. Hematogenous metastases showed more alterations than lymph node tumors, particularly more deletions at 1p, 3, 4, 5q, 10q, 14, and 21q21 and gains at 1q, 7p, 12qter, 13, 16, and 22q. Comparing liver metastases with their corresponding primary tumors, particularly deletions at 2q, 5q, 8p, 9p, 10q, and 21q21 and gains at 1q, 11, 12qter, 17q12-q21, 19, and 22q were more often observed. The analysis suggested that the different pathways of tumor dissemination are reflected by a nonrandom accumulation of chromosomal alterations with specific changes being responsible for the different characteristics of the metastatic phenotype.     

Nonrandom secondary chromosome-aberrations in liposarcomas with t(12, 16)

Ten liposarcomas were analyzed cytogenetically after short-term culturing. Eight tumors had a t(12;16) (q13;p11) and two tumors had complex translocations involving chromosomes 7, 12, and 16 and 2, 9, 12, 16 and 20, respectively. Among the secondary aberrations seen in five tumors, +8 was found in two tumors and i(7)(q10) in four tumors. Trisomy 8 has previously been described as a nonrandom secondary aberration in myxoid liposarcoma, but i(7q) has only been reported in a single case before. All recurrent chromosome aberrations reported in liposarcomas with recombination between 12q13 and 16p11 (42 cases) were surveyed and compared with their frequencies in liposarcomas without this recombination (33 cases). Trisomy 5 and 8 were found in both tumor groups, whereas +19, t(3;15)(p23;q15), del(6)(q21), i(7q), and rearrangements of 1p11 and 2q35 were found exclusively in tumors with 12q13 and 16p11 aberrations.     

Simultaneous occurrence of a T-cell lymphoma and a chronic myelogenous leukemia with an unusual karyotype

The simultaneous occurrence of malignant T-cell lymphoma and chronic myelogenous leukemia is reported. The lymph nodes contained E rosette forming cells. Blood and bone marrow cell morphology were consistent with the diagnosis of chronic myelogenous leukemia. Lymph nodes, bone marrow and blood mitosis showed a t(6;8) (6pter→6q27 ::8p12→8pter;6qter→6q27 ::8p12→8qter) translocation.So far a number of recent reports have shown simultaneous B lymphoid and myeloid proliferations in some malignancies, this is apparently the first reported case of simultaneous T lymphoid and myeloid proliferations.     

Cytogenetic findings in 14 benign cartilaginous neoplasms

Benign cartilaginous tumors represent a spectrum of neoplastic processes with variable clinical and pathologic presentations. These tumors are histologically characterized by the presence of chondrocytes surrounded by a cartilaginous matrix. Few studies describe karyotypic abnormalities in these benign lesions. We report a series of 14 chondromas from a single institution. Conventional cytogenetics was performed on short term cultures from all cases. Clonal chromosome aberrations were found in nine tumors. One soft tissue chondroma contained three clones with t(6;12)(q12;p11.2), t(3;7)(q13;p12), and der(2)t(2;18)(p11.2;q11.2). Three periosteal chondromas displayed random structural aberrations of chromosomes 2, 3, 6, 7, and 11 and loss of chromosome 13. Among the enchondromas, three tumors displayed chromosome losses, one contained a complex translocation involving chromosomes 12, 15, and 21 as well as an inv(2)(p21q31),t(12;15;21)(q13;q14;q22) and a separate enchondroma showed a translocation involving chromosomes 12 and 22. Our data suggest that considerable cytogenetic heterogeneity exists among benign chondromatous tumors.     

A complex karyotype involving chromosomes 3, 6, 11, 12, and 22 in adult acute lymphoblastic leukemia

Complex chromosomal abnormalities are rare in adult patients with acute lymphoblastic leukemia (ALL). Using molecular methods, we characterized a complex karyotype involving chromosomes 3, 6, 11, 12, and 22 in a 38-year-old man with ALL. Cytogenetic analysis revealed the following karyotype: 46,XY,der(3)t(3;?6)(q22;?p21), - 6,add(11)(q23),add(12)(p13), + mar[10]/46,XY[19]. Because patients with 11q23 abnormalities have a poor prognosis and require aggressive treatment, we used fluorescence in situ hybridization (FISH) to fully characterize the abnormalities. FISH analysis showed no rearrangement of the MLL or ETV6-CBFA2 (TEL-AML1) genes; the wild-type ETV6 allele was deleted in most cells. The revised karyotype after the FISH analysis was as follows: 46,XY,der(3)t(3;12)(p13;p?13)del(3)(q21),der(6)inv(6)(p21q21)ins(6;3)(q21;q21q25),der(11)t (3; 11)(q25;q23),der(12)t(11; 12)(q23;p?12),t(12;22)(p13;q13). Although structural abnormalities involving 11q23 and 12p13 bands were identified by conventional cytogenetics, this report clearly demonstrates that molecular assays are needed to fully characterize gene rearrangements, complex translocations as well as to assign patients to the appropriate treatment group.     

Interphase cytogenetic abnormalities in chronic lymphocytic leukemia may predict response to rituximab

Select cytogenetic abnormalities such as del(17)(p13.1) and del(11)(q22-q23)predict rapid disease progression and inferior survival in chronic lymphocytic leukemia (CLL). We sought to determine the impact of the four most common interphase cytogenetic abnormalities in 28 CLL patients relative to response to three-times-a-week rituximab therapy. Abnormalities were noted in 25 of the 28 patients to include del(13)(q14.3) [n = 16 (57%)], del(11)(q22.3) [n = 10 (36%)], +12 [n = 6 (21%)], del(17)(p13.1) [n = 5 (18%)], and normal [n = 3 (11%)]. Only a minority of each of these occurred as sole abnormalities. To categorize patients into one specific group, we used the hierarchical order del(17)(p13.1) > del(11)(q22.3) > trisomy 12 > del(13)(q14.3) to prioritize. Response to rituximab was noted to vary by cytogenetic group: del(17)(p13.1), 0% [n = 5]; del(11)(q22.3), 66% [n = 9]; del(13)(q14.3), 86% [n = 7]; +12, 25% [n = 4], and normal, 0% [n = 3]. Response was significantly lower (P = 0.05) in patients with del(17)(p13.1) as compared with those with other abnormalities. These data suggest that interphase cytogenetics in CLL may be predictive of a response to rituximab therapy and provide support for additional studies validating risk-adapted therapy in this disease.     

伴t(11;19)(q23;p13.1)恶性血液病的临床和实验室特征

目的 探讨伴t(11;19) (q23;p13.1)恶性血液病的临床及实验室特征.方法 分析1例血液病患者资料,其骨髓细胞24 h培养后按常规方法制备染色体,用R显带技术进行细胞遗传学分析.结果 该例患者核型为t(11;19) (q23;p13.1),确诊为急性髓系白血病(AML)-M4c.应用MA方案化疗后患者未获完全缓解.结论 t(11;19)(q23;p13.1)是一类很独特的白血病亚型有关的易位,为少见的非随机染色体易位,其临床预后差.     

A complex translocation t(5;9;22) in Philadelphia cells involving the short arm of chromosome 5 in a case of chronic myelogenous leukemia

Chronic myelogenous leukemia (CML) is genetically characterized by the reciprocal translocation of chromosome 9 and 22, t(9;22)(q34;q11) which results in the fusion of BCR/ABL gene observed on the derivative chromosome 22 called Philadelphia (Ph') chromosome. About 5-8% of Philadelphia positive patients with CML show various complex translocations involving one or more other chromosomes, in addition to chromosome 9 and 22. In our report we discuss one case with CML, his cytogenetic study revealed a complex translocation t(5;9;22)(p15.1; q34; q11.2), del 5p15.1-->pter, translocation BCR(22q11.2-->qter) to der(5), positive Ph-chromosome and positive t(BCR\ABL). Further confirmation of complex translocation was done by FISH study using the LSI BCR/ABL dual color dual fusion (DF) translocation probe, chromosome 5 and 22 whole paint probes.     

Karyotypic abnormalities in adenocarcinomas of the lung

Cytogenetic analysis of 114 adenocarcinomas of the lung revealed clonal abnormalities in 67 tumors. The chromosome numbers ranged from near-diploid to hypertetraploid. Clonal abnormalities seen as the sole anomaly were loss of the Y chromosome (21 tumors), trisomy 7 (2 tumors), and trisomy 12 (1 tumor). A supernumerary ring chromosome was the only clonal change in 4 tumors. The bands most often affected were 17p11-13 (13 cases), 1q10-12 and 1p22 (10 cases each), 1p11-13 and 1q21 (9 cases each), and 11p11, 11p15 and 15p11-13 (6 cases each). The chromosomes most frequently involved in structural rearrangements were chromosomes 1 (30 cases), 11 (20 cases), 3 (17 cases), 17 and 7 (16 cases each). Repeated loss of material from chromosome arms 1p, 3p, 6q, 11p, and 17p and gains of 1q were found. Recurrent structural changes were del(1)(p22) and i(5)(p10) (5 cases each) i(1)(q10), i(13)(q10), i(14)(q10) and del(17)(p11) (3 cases each). We found no abnormalities that seemed to be specifically associated with pulmonary adenocarcinomas, but isochromosomes i(1)(q10), i(5)(p10) and i(13)(q10) and changes of 6q were present in our series at frequencies higher than those generally seen in the other main types of lung cancer.     

Report of novel chromosomal abnormalities in a series of 130 chronic lymphocytic leukemia patients studied by classic cytogenetic analysis

One-hundred-and-thirty typical, unselected CLL cases were studied by conventional cytogenetic analysis. Seventy-three patients (56.2%) had normal karyotype ('normal sub-group'), while 57/130 patients (43.8%) had abnormal karyotype. Twenty-two of 57 patients (38.6%) carried more than one abnormality. Six novel chromosomal abnormalities were detected in five patients: (i) t(3;13)(q14;q34); (ii) t(Y;11)(q12;q23), del(13)(q12q14); (iii) dic(3;11)(p21;q23); (iv) t(3;5)(q29;q23); (v) t(3;22) (p21;q13); and (vi) t(1;13)(p12;q12). Three of five patients carrying novel translocations had progressive disease. The true biological and clinical significance of novel chromosomal abnormalities remains to be determined.