Cytogenetic characteristics of childhood non-Hodgkin lymphoma.

Cytogenetic studies were performed successfully on 24 patients with non-Hodgkin lymphoma (NHL) who were younger than 15 years of age. Of these, 22 patients (92%) had abnormal clones. With respect to histologic findings, 3 (25%) of the 12 patients with lymphoblastic lymphoma had 14q11 translocations and 2 (17%) had t(9;17) (q34;q23). Four (80%) of the five patients with small non-cleaved cell lymphoma had t(8;14)(q24;q32). With respect to immunologic findings, four (44%) of the nine patients with T-cell lymphoma had abnormalities consisting of 14q11 and 7q36 translocations, in which the T-cell receptor genes resided. Three (33%) of the patients with T-cell lymphoma had t(9;17)(q34;q23). However, three (43%) of the seven patients with B-cell lymphoma had t(8;14) (q23;q32), and two (29%) of the patients with B-cell lymphoma had an extra i(11q) chromosome with a resultant 11q tetrasomy. Non-T-cell non-B-cell lymphomas, which occurred in 21% of all patients, showed various chromosomal abnormalities. This study demonstrated that, in childhood NHL, karyotype correlates closely with immunophenotype, clinical features, and histologic findings.     

Chromosomal abnormalities in patients with non-cutaneous T-cell non-Hodgkin's lymphoma

In contrast to non-Hodgkin's lymphomas (NHL) with a B-cell phenotype, almost no data have been reported dealing with correlations between chromosomal abnormalities and characteristics of the disease in patients with T-cell NHL. In a retrospective analysis we studied all patients with a non-cutaneous T-cell NHL and chromosomal abnormalities that were evaluated at our institution; 20 patients could be identified. Numerical abnormalities involving chromosomes 3, 4, 5, 22 and X were observed most frequently. Structural abnormalities involved mainly the breakpoints 1q22–25, 6q23 and 11q13. There appeared to be an association between +7 breakpoints 2p23–24, 4p14–15, 8q21 and the presence of extranodal disease. All patients with +7 had a diffuse mixed histology. Patients with +2, +3, +11, +17, +18, +20 or breakpoint 1q22–25 had an immunoblastic lymphoma and patients with breakpoints 9q32–34 or 14q12 had a lymphoblastic lymphoma. No correlations were observed between chromosomal abnormalities and response to therapy, survival or phenotypic markers. Abnormalities involving the chromosomes containing the T-cell receptor genes and T-cell markers were infrequent. Several breakpoints were identified that correlate with already described oncogenes.     

Cytogenetics of non-Hodgkin's lymphoma

In the non-Hodgkin's lymphoma (NHL), recurring cytogenetic abnormalities have been identified, and significant correlations among them and morphology, immunophenotyping, and parameters of clinical outcome have been recognized. The structural involvement of the 14q32 band is substantially more frequent than are other common abnormalities, which include del(6q), i(17q), +3, +7, +12, +18, and +21. Twenty-two recurring translocations have been identified. Almost three-fourths of all breakpoints in NHL occur at sites to which lineage-determining, transformation-related genes, or fragile sites have been mapped. Besides the well-known association of the t(14;18) (q32;q21) with the follicular histologies and t(8;14)(q24;q32) with small non-cleaved cell lymphoma, several other associations between recurring cytogenetic abnormalities and morphologic subtypes have been found. Similarly, several associations between cytogenetic abnormalities and the B or T immunophenotype have been delineated. Trisomy 3 or duplications of 3p predict a favorable clinical outcome; trisomy 2 or duplication 2p and abnormalities of chromosome 17 predict a poor prognosis. Common sequential changes include a (second) 14q32 break and abnormalities of chromosomes 1 and 2. Continuing work in these areas will serve to identify more clearly those regions of the genome important to transformation, differentiation, clinical aggressiveness, and progression in NHL.     

New recurrent structural chromosome aberrations in non-Hodgkin's lymphoma

Identification, and subsequent molecular dissection, of recurring structural chromosome aberrations has led to a substantial increase in our understanding of lymphomagenesis. Thus we have reviewed the published literature on cytogenetic findings in non-Hodgkin's lymphoma (NHL) in search of previously unrecognized recurring chromosome aberrations. Thirty-four balanced rearrangements, including 32 reciprocal translocations and two inversions, and 25 unbalanced translocations, each observed in at least two different cases of NHL and previously unrecognized as recurring, have been ascertained. Among the 32 reciprocal translocations, 10 involved bands harboring one of the immunoglobulin (Ig) genes. In nine of these, the following bands or regions may be sites of putative oncogenes that are activated through juxtaposition to Ig loci: 1p35-36, 5q11, 6q21, 9p24, 12q13, 13q11, 15p11, 15q21-22 and 15q23-24. In one instance, t(21;22)(q22;q11), Ig lambda chain gene involvement is unlikely, because the t(21;22) has been identified in two NHLs of T-cell lineage. An additional four reciprocal translocations and one inversion affected the band 3q27, containing the BCL6/LAZ3 gene, and one of the following bands: 1q25, 3q12, 6p21, 7p13, 12p13. Three other reciprocal translocations had the breakpoint at 11q13 known to harbor the BCL1 gene. Among the 16 remaining balanced rearrangements, one translocation involved a band containing a gene for a T-cell receptor, i.e. 7q35. Almost all chromosomes in the human karyotype (except 3, 8, 20 and 21) were implicated in at least one of the 25 recurrent unbalanced translocations. The distribution of resulting chromosomal imbalances is highly nonrandom, however, because 17 translocations involved the long arm of chromosome 1 (1q) invariably resulting in partial trisomy of 1q. We suggest that these unbalanced translocations of Iq are best regarded as non-specific secondary abnormalities that may contribute to lymphoma progression.     

Chromosome abnormalities in adult T-cell leukemia/lymphoma: a karyotype review committee report.

Karyotypes of 107 cases with adult T-cell leukemia/lymphoma (58 male, 49 female; 81 acute or lymphoma type, 26 chronic or smoldering type) were reviewed by a panel of cytogeneticists and were correlated with the subtypes of the disease. Clonal chromosome abnormalities were found in 103 (96%) cases, of which four had hypotetraploidy. Of 184 numerical abnormalities in the remaining 99 cases with near- or pseudodiploidy, trisomies for chromosomes 3 (21% of cases), 7 (10%), and 21 (9%), monosomy for X chromosome (38%) in the female, and loss of a Y chromosome (17%) in the male were more frequent than expected (P less than 0.01). Of 373 structural abnormalities in all the 103 aneuploid cases, translocations involving 14q32 (28%) or 14q11 (14%) and deletion of 6q (23%) were most frequent, followed by deletion of 10p (9%), 3q (8%), 5q, 9q, and 13q (7% each), and 1p and 7p (6% each). The proportion of cases with aneuploid clones (with greater than or less than 46 chromosomes), the average numbers per case of both numerical and structural abnormalities, and marker chromosomes were larger in the aggressive acute or lymphoma type than in the nonaggressive chronic or smoldering type (P less than 0.01). The combination of rearrangement in 14q32 and monosomy X (seven cases) or deletion of 10p (six cases), and that of trisomy 3 and deletion in 6q21 (six cases), occurred only in the acute or lymphoma type and may be associated with the aggressiveness in adult T-cell leukemia/lymphoma.     

Change in a complex translocation involving band 7q34 and 9p- in a case of T-cell lymphoblastic lymphoma

The authors report a case of T-cell type non-Hodgkin's lymphoma (NHL) in which neoplastic cells possessed a three-way translocation involving chromosomal bands 3q21, 7q34, and 22q11, as well as partial monosomy of the short arm of chromosome 9. In the literature, most reported cases of 7q32-q36 abnormalities had T-cell type leukemia/lymphoma and were younger than 20 years. Two NHL cases, including the current case, were diagnosed as having lymphoblastic lymphoma with a leukemic transformation. The neoplastic cells of the reported cases commonly showed CD2 (E-rosette receptors) and CD38. All 17 patients but three manifested a mediastinal mass at diagnosis and seven had central nervous system lesions or pleural infiltration. Furthermore, five of the 19 reported cases also showed 9p- change.     

The utility of t(14;18) in understanding risk factors for non-Hodgkin lymphoma

Characteristic chromosomal abnormalities are associated with specific histological subtypes of non-Hodgkin lymphoma (NHL). The chromosomal translocation t(14;18)(q32;q21) is one of the most common chromosomal abnormalities in NHL, occurring in 70%-90% of cases of follicular lymphoma, 20%-30% of diffuse large B-cell lymphoma, and 5%-10% of other less common subtypes. The t(14;18)-positive NHL may represent a homogenous group and, consequently, increase etiologic specificity in epidemiological studies. Although the t(14;18) has important clinical ramifications, its etiologic significance remains to be determined. Two population-based, case-control studies addressed this issue by evaluating potential risk factors for t(14;18)-positive and t(14;18)-negative subgroups of NHL. Both studies found that the association between pesticide exposures and risk of NHL was largely limited to t(14;18)-positive NHL cases. However, the findings regarding cigarette smoking, family history of hematopoietic cancer, and hair dye use were not entirely consistent. These results indicate that defining subgroups of NHL according to t(14;18) status may be useful for etiologic research, particularly for exposures that are genotoxic or may contribute to the development of NHL through pathways involving the t(14;18). Studies to further evaluate these associations and delineate the effects of various exposures in other genetically defined subgroups of NHL are warranted.     

Centrosome aberrations as a possible mechanism for chromosomal instability in non-Hodgkin's lymphoma.

Recently, centrosome aberrations have been described as a possible cause of aneuploidy in many solid tumors. To investigate whether centrosome aberrations occur in non-Hodgkin's lymphoma (NHL) and correlate with histologic subtype, karyotype, and other biological disease features, we examined 24 follicular lymphomas (FL), 18 diffuse large-B-cell lymphomas (DLCL), 33 mantle cell lymphomas (MCL), and 17 extranodal marginal zone B-cell lymphomas (MZBCL), using antibodies to centrosomal proteins. All 92 NHL displayed numerical and structural centrosome aberrations as compared to nonmalignant lymphoid tissue. Centrosome abnormalities were detectable in 32.3% of the cells in NHL, but in only 5.5% of lymphoid cells from 30 control individuals (P<0.0001). Indolent FL and MZBCL contained only 25.8 and 28.8% cells with abnormal centrosomes. In contrast, aggressive DLCL and MCL harbored centrosome aberrations in 41.8 and 35.0% of the cells, respectively (P<0.0001). Centrosomal aberrations correlated to lymphoma grade, mitotic, and proliferation indices, but not to the p53 labeling index. Importantly, diploid MCL contained 31.2% cells with abnormal centrosomes, while tetraploid samples harbored centrosome aberrations in 55.6% of the cells (P<0.0001). These results indicate that centrosome defects are common in NHL and suggest that they may contribute to the acquisition of chromosomal instability typically seen in NHL.     

A pathologic study of childhood lymphoma in Taiwan with special reference to peripheral T-cell lymphoma and the association with Epstein-Barr viral infection.

The authors retrospectively reviewed the clinicopathologic and immunologic features of 65 consecutive cases of childhood lymphoma reported between 1980 and 1989. Southern blot hybridization was also performed in 23 cases to study their association with Epstein-Barr virus (EBV) and human T-cell leukemia virus type 1 (HTLV-1). The 65 cases included 56 non-Hodgkin's lymphoma (NHL) (86%) and 9 Hodgkin's disease (HD) (14%). The NHL could be classified into the following groups: Group I, small noncleaved cell lymphoma (20 cases); Group II, lymphoblastic lymphoma (17 cases); Group III, large cell lymphoma (17 cases); and miscellaneous (2 cases). There was no follicular lymphoma case. Immunohistochemical study on paraffin sections and/or frozen specimens in 47 cases of NHL showed that all the Group I cases belonged to B-cell neoplasm (17 of 17 cases); most of the Group II cases belonged to T-cell neoplasm (9 of 14 cases); and most of the Group III cases were peripheral T-cell lymphoma (PTL) (8 of 16 cases), including 2 cases of Ki-1 lymphoma. The majority of childhood NHL belonged to high-grade malignancy with an aggressive clinical course (median survival time, 8 months). The EBV DNA could be detected from the tumor tissues in 4 of 6 PTL, but in none of the remaining 19 cases of NHL including 6 Burkitt's type lymphomas. HTLV-1 proviral genome was not detected in all specimens examined. The authors concluded that the distribution pattern and clinicopathologic feature of childhood lymphoma in Taiwan are comparable to that in Japan and western countries. The frequent association of EBV with aggressive PTL was unique and deserves additional investigation.     

Predictive role of interphase cytogenetics for survival of patients with multiple myeloma.

PURPOSE: Recent metaphase cytogenetic studies suggested that specific chromosomal abnormalities are of prognostic significance in patients with multiple myeloma (MM). Because the true incidence of chromosomal abnormalities in MM is much higher than that detected by metaphase analysis, we used interphase fluorescence in situ hybridization (FISH) to determine the prognostic value of specific chromosomal aberrations. PATIENTS AND METHODS: Bone marrow plasma cells from 89 previously untreated patients with MM were studied consecutively by FISH to detect the deletions of 13q14, 17p13, and 11q and the presence of t(11;14)(q13;q32). FISH results were analyzed in the context of clinical parameters (response to treatment and survival after conventional-dose chemotherapy), and a multivariate analysis of prognostic factors was performed. RESULTS: By FISH, the deletion of 13q14 occurred in 40 patients (44.9%), deletion of 17p13 in 22 (24.7%), and 11q abnormalities in 14 (15.7%; seven with t(11;14)). Deletions of 13q14 and 17p13 were associated with poor response to induction treatment (46.9% v 77.3% in those without deletions, P =.006 and 40.0% v 73.2%, P =.008, respectively) and short median overall survival (OS) time (24.2 v 88.1 months, P =. 008 and 16.2 v 51.3 months, P =.008, respectively). Short median OS time was also observed for patients with 11q abnormalities (13.1 v 41.6 months, P =.02). According to the number of unfavorable cytogenetic features (deletion of 13q14, deletion of 17p13, and aberrations of 11q) that were present in each patient (0 v 1 v 2 or 3), patients with significantly different OS times could be discriminated from one another (102.4 v 29.6 v 13.9 months, P <.001, respectively). CONCLUSION: For patients with MM who were treated with conventional-dose chemotherapy, interphase FISH for 13q14, 17p13, and 11q provides prognostically relevant information in addition to that provided by standard prognostic factors. This observation may be considered for risk-adapted stratifications of MM patients in future clinical trials.     

Cytogenetic and immunohistochemical analysis of lymphoepithelioid cell lymphoma (Lennert's lymphoma): further substantiation of its T-cell nature

In 1968 a special variant of Hodgkin's disease, epithelioid cellular lymphogranulomatosis--later on termed lymphoepithelioid cell lymphoma/Lennert's lymphoma--was defined. There are increasing indicators that Lennert's lymphoma is of T-cell origin. Seven cases of Lennert's lymphoma are studied with cytogenetic as well as immunohistochemical techniques. Six of them have cytogenetic abnormal clones always including aberrations of chromosome No. 3 (+3, break in q22, dup q22----q24). In all cases band 3q22 is either broken or duplicated. Immunohistochemically it is clearly demonstrated that the proliferating cells are of T-cell nature (Ki67+, Leu4+, Leu1+). Under consideration in the literature it can be stated in conclusion that (1) lymphoepithelioid cell lymphoma (Lennert's lymphoma) with aberrations has to be designated as malignant lymphoma, (2) immunohistochemical double labeling proved the T-cell nature of this lymphoma, (3) there are remarkable similarities between the chromosomal patterns of lymphoepithelioid cell lymphoma, lymphogranulomatosis X/angioimmunoblastic lymphadenopathy and probably Hodgkin's disease: many normal mitoses and abnormalities of chromosome No. 3, especially trisomy. It is discussed that abnormalities of chromosome No. 3 involving band q22 are an indicator of a common genetic background of these lymphomas.     

Loss of chromosome 11q21-23.1 and 17p and gain of chromosome 6p are independent prognostic indicators in B-cell non-Hodgkin's lymphoma.

Comparative genomic hybridization (CGH) was employed to study chromosomal aberrations in relation to cell proliferation, apoptosis, and patient survival in 94 cases of B-cell non-Hodgkin's lymphoma diagnosed between 1983 and 1993. Eighty cases had aberrations by CGH. Chromosomal regions 1p21-31.1 (10%), 6cen-q24 (12%), 8p (11%), 9p21-ter (14%), 11q21-23.1 (11%), 13q13-21.1 (12%), and 17p (15%) were frequently lost. Gains were found at 3q21-ter (22%), 6p (11%), 7p (12%), 8q23-ter (13%), 12cen-q15 (17%), 17q24-ter (13%), and 18q13.3-21 (20%). A high number of aberrations (> or = 4, 33 cases) was associated (P < or = 0.001) with the mantle cell and diffuse large B-cell lymphoma subtypes, a high fraction of tumour cells in S phase, and short survival (RR (relative risk) = 3.7). Loss of 1p21-31.1, 8p, 9p21-ter, 11q21-23.1, and 13q13-21.1 were associated with mantle cell lymphoma (P < or = 0.03), while gain of 6p and 12cen-q15 were more frequent in diffuse large B-cell and small lymphocytic lymphoma, respectively (P = 0.04). Loss of 8p and 17p, and gain of 3q21-ter, 6p, 7p, and 8q23-ter were associated with a high S phase fraction (P < or = 0.03), but none of the aberrations were associated with tumour apoptotic fraction (P > or = 0.13). The most important prognostic CGH parameters (P < 0.001) were losses of 11q21-23.1 (RR = 3.8) and 17p (RR = 4.4), and gain of 6p (RR = 4.2). The latter parameters and IPI were the only ones with independent prognostic value (RR = 10, 5.0, 6.7, and 3.7, respectively; P < 0.001) when assessed together with lymphoma sub-type, primary versus relapse cases, treatment, B symptoms, S phase fraction, and presence of BCL1 and BCL2 translocations. A combined CGH/IPI binary parameter had high prognostic value for patients receiving different treatments, with various lymphoma sub-types, and for primary as well as relapse cases.     

Specific chromosomal aberrations in de novo acute myeloid leukemia: a comparative analysis of results with a report of three novel chromosomal rearrangements t(7;14)(q35;q13), t(8;18)(p11.2;q12), t(13;15) in Indian population

Background: Acute myeloid leukemia (AML) is a heterogeneous disease with regard to morphology, immunophenotype, and genetic rearrangements. Multiple recurrent chromosomal aberrations have been identified by conventional cytogenetic analysis, which is now widely recognized as one of the most important diagnostic and prognostic determinants in AML. Method: Conventional cytogenetic analysis was done on 200 de novo AML subjects. Results: Of these, 176 (88%) were successfully karyotyped and 24 (12%) showed culture failure. Among the176 subjects, 101 (57.4%) were abnormal and 75 (42.6%) showed an apparently normal karyotype. The various aberrations observed were t(8;21)(q22;q22) (5.2%); t(15;17) (q22;q11-21) (9%); t(9;22)(q34;q11)(1.7%); t(14;17)(q32;q11.2)(0.5%); inv(16)(p13;q22)(1.7%); 11q23 rearrangements (4%); monosomy 7 (2.2%) and 22 (1.1%); deletion of 9q (q22q34) (5.1%), 5q (q13q33) (0.5%) and 13q (q13q31) (0.5%); common trisomies like +8 (5.6%), +16 (1.7%), +22 (1.1%), +21 (0.5%), +13 (0.5%), +11 (0.5%), +3 (0.5%); hyperdiploidy (3.4%); hypodiploidy (1.1%); complex karyotype (4%); and other structural abnormalities (4.5%). Apart from these, three novel chromosomal abnormalities viz. t(8;18), t(7;14), t(13;15) were observed in the current study population. Conclusion: This study confirms that the incidence of chromosomal abnormalities varies considerably. Comparatively, the incidence t(15;17), and del9q is higher, while that of −5/del5q, −7/del7q and inv (16) were lower in our population. Similarly, the frequency of other recurrent FAB associated abnormalities viz. 11qabn was comparable to previous reports. Furthermore, ongoing cytogenetic studies are warranted in larger groups of AML cases to identify newly acquired chromosomal aberrations that may aid in cloning novel genes involved in the neoplastic process, ultimately helping in the development of targeted therapeutic drugs.     

Specific chromosomal aberrations in de novo acute myeloid leukemia: A comparative analysis of results with a report of three novel chromosomal rearrangements t(7;14)(q35;q13), t(8;18)(p11.2;q12), t(13;15) in Indian population

Background: Acute myeloid leukemia (AML) is a heterogeneous disease with regard to morphology, immunophenotype, and genetic rearrangements. Multiple recurrent chromosomal aberrations have been identified by conventional cytogenetic analysis, which is now widely recognized as one of the most important diagnostic and prognostic determinants in AML. Method: Conventional cytogenetic analysis was done on 200 de novo AML subjects. Results: Of these, 176 (88%) were successfully karyotyped and 24 (12%) showed culture failure. Among the176 subjects, 101 (57.4%) were abnormal and 75 (42.6%) showed an apparently normal karyotype. The various aberrations observed were t(8;21)(q22;q22) (5.2%); t(15;17) (q22;q11-21) (9%); t(9;22)(q34;q11)(1.7%); t(14;17)(q32;q11.2)(0.5%); inv(16)(p13;q22)(1.7%); 11q23 rearrangements (4%); monosomy 7 (2.2%) and 22 (1.1%); deletion of 9q (q22q34) (5.1%), 5q (q13q33) (0.5%) and 13q (q13q31) (0.5%); common trisomies like +8 (5.6%), +16 (1.7%), +22 (1.1%), +21 (0.5%), +13 (0.5%), +11 (0.5%), +3 (0.5%); hyperdiploidy (3.4%); hypodiploidy (1.1%); complex karyotype (4%); and other structural abnormalities (4.5%). Apart from these, three novel chromosomal abnormalities viz. t(8;18), t(7;14), t(13;15) were observed in the current study population. Conclusion: This study confirms that the incidence of chromosomal abnormalities varies considerably. Comparatively, the incidence t(15;17), and del9q is higher, while that of −5/del5q, −7/del7q and inv (16) were lower in our population. Similarly, the frequency of other recurrent FAB associated abnormalities viz. 11qabn was comparable to previous reports. Furthermore, ongoing cytogenetic studies are warranted in larger groups of AML cases to identify newly acquired chromosomal aberrations that may aid in cloning novel genes involved in the neoplastic process, ultimately helping in the development of targeted therapeutic drugs.     

Malignant lymphoma in southern Taiwan according to the revised European-American classification of lymphoid neoplasms

BACKGROUND: The purpose of the current study was to determine the distribution and relative frequency of each subtype of malignant lymphoma in southern Taiwan according to the revised European-American classification of lymphoid neoplasms (REAL). METHODS: The pathology files of a regional hospital in southern Taiwan for 1989-1998 were searched for malignant lymphoma, lymphoproliferative disorder, and Hodgkin disease (HD). The results of light microscopy, immunohistochemistry, and in situ hybridization for Epstein-Barr virus-encoded RNA (EBER) were correlated with clinical findings, and all cases were classified according to REAL. RESULTS: A total of 205 cases were analyzed retrospectively. There were 197 cases (96.1%) of non-Hodgkin lymphoma (NHL) and 8 cases (3. 9%) of HD. Among the 197 NHL cases, 161 (81.7%) were of B-cell lineage and 36 (18.3%) were of T-/natural killer cell lineage. Diffuse large B-cell lymphoma, extranodal marginal zone lymphoma, and follicular lymphoma were the most common B-cell subtypes and represented 47.2%, 19.3%, and 6.1%, respectively, of all NHL cases. Among the 36 cases of T-/natural killer cell lineage, unspecified peripheral T-cell lymphoma (8.6%), T-/natural killer cell lymphoma (angiocentric lymphoma) (4.1%), and anaplastic large cell lymphoma (3.6%) were the most common subtypes. Seven of eight T-/natural killer cell lymphoma cases were positive for EBER. The eight cases of HD were classified as lymphocyte-rich classic (two cases), nodular sclerosis (two cases), and mixed cellularity (four cases) subtypes. Three of these eight cases were positive for EBER. CONCLUSIONS: To the authors' knowledge this study is the first in Taiwan using the REAL classification and it again confirms the different geographic distribution of the various subtypes of malignant lymphoma. The frequency of T-/natural killer cell lineage NHL in Taiwan is higher than that in Western countries but not as high as reported previously.     

Non-Hodgkin's lymphomas with Burkitt-like cells are associated with c-Myc amplification and poor prognosis

Out of 344 patients with newly diagnosed non-Hodgkin's lymphoma (NHL), this study identified 16 patients presenting Burkitt-like cells (BLCs) after cytological and/or histological review. Conventional cytogenetic analysis showed at diagnosis complex chromosomal abnormalities in 13 cases and a normal karyotype in three cases. However, neither t(8;14)(q24;q32) nor the variants t(2;8)(p12;q24) or t(8;22)(q24;q11) was detected. FISH studies showed c-MYC amplification in all cases with four to more than seven copies in 10 - 77% metaphase or inter-phase cells. This study did not observe any gene fusion signal for c-MYC/IgH excluding a t(8;14) translocation and partial tri or polysomy of chromosome 8. It also excluded in that cases a break apart for the c-MYC locus. This study also never detected IgL/c-MYC, IgK/c-MYC or X-c-MYC. The BLCs were present whatever the lymphoma sub-type: follicular lymphoma (FL) was diagnosed in six out of 16 patients, mantle cell lymphoma (MCL) in four out of 16 patients, marginal zone lymphoma (MZL) in two out of 16 patients and diffuse large B-cell lymphomas (DLBCL) in three out of 16 patients. One additional patient presented a T-cell lymphoma. The clinical course was aggressive with a poor prognosis, as death occurred in nine patients, within 6 months after diagnosis for eight of them. These data could suggest a sub-group of NHL patients (15 B-NHL, 1 T-NHL) have been identified with a poor prognosis characterized by the association of Burkitt-like cells and c-MYC amplification without t(8;14)(q24;q32) or its variants. The possibility that this profile may represent a distinct morphologic NHL sub-set remains to be determined on a large cohort of patients.     

Fluorescence in situ hybridization analysis of chromosome aberrations in 60 Chinese patients with multiple myeloma

Conventional cytogenetic analysis is often hampered owing to the low mitotic index of multiple myeloma (MM) cells in bone marrow samples of MM. Interphase fluorescence in situ hybridization (I-FISH) analysis combined with magnetic-activated cell sorting (MACS) has substantially enhanced the sensitivity of cytogenetic analysis. Here, we used I-FISH to explore the incidence of chromosomal abnormalities in 60 Chinese patients with newly diagnosed MM. Five different specific probes for the regions containing 13q14.3 (D13S319), 14q32 (IGHC/IGHV), 1q21, 1p12, and 17p13 were used to detect chromosomal aberrations, and LSI IGH/CCND1, LSI IGH/FGFR3, and LSI IGH/MAF probes were further applied to detect t(11;14)(q13;q32), t(4;14)(p16;q32), and t(14;16)(q32;q23) in patients with 14q32 rearrangement. Fifty of the patients (83.3%) had at least one type of abnormalities regarding the regions analyzed. Nine patients (15%) had one abnormality; 10 patients (16.7%) had two abnormalities; 31 patients (51.7%) had three or more abnormalities. The most frequent abnormality in the patients was illegitimate IgH rearrangement (70%), followed by 13q14 deletion (63.3%), 1q21 amplification (61.7%), 1p12 deletion (33.3%), and 17p13 deletion (13.3%). These aberrations are not randomly distributed, but strongly interconnected. Patients with 17p13 deletion or t(4;14)(p16;q32) had significant higher ??2-microglobulin level (P?<?0.05). However, all these abnormalities had no correlation with age, gender, disease stage, and Ig isotype; yet, it was showed that the frequencies of the individual chromosomal abnormalities were very high. Taken together, MACS in combination with I-FISH may be a promising tool to detect the molecular cytogenetic abnormalities of MM.     

Translocation t(3;22)(q23;q11) in three patients with diffuse large B cell lymphoma

In our series of 134 patients with a diagnosis of non-Hodgkin's lymphoma (NHL) and clonal chromosomal abnormalities, three were found to show an identical t(3;22)(q28;q11) translocation. All were old patients with isolated lymphadenomegaly and diffuse large noncleaved cell lymphoma. All expressed a B cell immunophenotype, and all entered a complete remission when treated with aggressive chemotherapy. This translocation could, therefore, delineate a particular subtype of diffuse large cell NHL.     

Molecular cytogenetic study of 126 unselected T-ALL cases reveals high incidence of TCRbeta locus rearrangements and putative new T-cell oncogenes.

Chromosomal aberrations of T-cell receptor (TCR) gene loci often involve the TCRalphadelta (14q11) locus and affect various known T-cell oncogenes. A systematic fluorescent in situ hybridization (FISH) screening for the detection of chromosomal aberrations involving the TCR loci, TCRalphadelta (14q11), TCRbeta (7q34) and TCRgamma (7p14), has not been conducted so far. Therefore, we initiated a screening of 126 T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma cases and 19 T-ALL cell lines using FISH break-apart assays for the different TCR loci. Genomic rearrangements of the TCRbeta locus were detected in 24/126 cases (19%), most of which (58.3%) were not detected upon banding analysis. Breakpoints in the TCRalphadelta locus were detected in 22/126 cases (17.4%), whereas standard cytogenetics only detected 14 of these 22 cases. Cryptic TCRalphadelta/TCRbeta chromosome aberrations were thus observed in 22 of 126 cases (17.4%). Some of these chromosome aberrations target new putative T-cell oncogenes at chromosome 11q24, 20p12 and 6q22. Five patients and one cell line carried chromosomal rearrangements affecting both TCRbeta and TCRalphadelta loci. In conclusion, this study presents the first inventory of chromosomal rearrangements of TCR loci in T-ALL, revealing an unexpected high number of cryptic chromosomal rearrangements of the TCRbeta locus and further broadening the spectrum of genes putatively implicated in T-cell oncogenesis.     

Frequent nonrandom chromosome abnormalities in 27 patients with untreated large cell lymphoma and immunoblastic lymphoma

Fresh tumor samples from 27 patients with large cell lymphoma, either previously untreated (26 patients) or minimally treated (one patient), were processed for cytogenetic studies. Cytogenetic abnormalities were observed in all patients, most commonly in chromosomes 1, 3, 7, 12, 14, 17, and 18. Nine chromosomal breakpoints appeared frequently: 14q32 in 14 instances; 18q21 in seven; 9p13-21, 17p11-13, and 3q21-23 in six each; 1p11-21 in five instances; 1p36 in four; and 2p21-23 in three. The most common structural abnormalities were t(14;18)(q32;q21) in seven patients (26%) and 17p- in six (22%). The presence of 17p- was associated with a significantly higher proliferative capacity as manifested by the percentage of S phase = 22% versus 11% for cases without 17p-(P less than 0.05). Trisomy 12, typical of small lymphocytic lymphoma, was seen in five patients in this series, all of whom had diffuse large cell lymphoma; frequently, it appeared simultaneously with t(14;18). The two patients with immunoblastic lymphoma of B-cell type had an abnormality involving chromosome 2p21-23. Deletions in the long arm of chromosome 6, previously described as typical of diffuse large cell lymphoma and B-cell immunoblastic lymphoma were observed infrequently in this series. However, this abnormality has been present in 50% of patients with large cell lymphoma previously exposed to therapy, suggesting that it may be related to effects of chemotherapy or to clonal evolution.