Biomedical subjects

S C Jhanwar

Publications and source records attributed to S C Jhanwar.

At least 73 records · Page 4Linked to original sources

PubMed1992

Malignant transformation of human melanocytes: induction of a complete melanoma phenotype and genotype.

Human melanoma provides a model to study malignant transformation and tumor progression. Expression of ras oncogenes in cultured normal human diploid melanocytes has induced a subset of phenotypic traits that are characteristic of malignant melanoma cells, including altered morphology, anchorage independence, induction of class II MHC antigens, up-regulation of the ganglioside GD3, and chromosomal abnormalities. However, other characteristics of melanoma, such as loss of expression of adenosine deaminase-binding protein and tumorigenicity, were not observed. We report here that melanocytes infected with a retrovirus containing the viral Ha-ras oncogene underwent complete transformation, acquiring all phenotypic characteristics of malignant melanomas observed in vivo. Transformation occurred in a sequential manner and was associated with spontaneous chromosomal instability. Cytogenetic analysis of transformed melanocytes indicated that the earliest structural chromosomal abnormalities were isochromosomes 6p and 9q followed by complete loss of chromosome 1p, all common karyotypic abnormalities described in human melanomas. The findings suggest that these chromosome regions which are deleted or relatively deficient may contain genes that are critical for the initiation and progression of the melanoma phenotype.

3T3 Cells↗

PubMed1991

Genetic alterations of the p53 gene are a feature of malignant mesotheliomas.

A putative tumor suppressor gene, p53, has been shown to be altered in a variety of human tumor types. The primary mechanism of p53 inactivation is believed to be mutation of one allele followed by loss of the second allele. Malignant mesothelioma is a tumor that has been highly associated with exposure to asbestos fibers, which are known to cause chromosomal abnormalities in mesothelial cells. We have examined four mesothelioma cell lines for genetic abnormalities in p53. Cytogenetic analysis revealed that two of the four tumors had abnormalities (numerical and/or structural) of chromosome 17 (the locus of the p53 gene). Restriction fragment length polymorphism analysis using a chromosome 17p-specific probe (pYNZ22) revealed that two tumors had loss of heterozygosity in the region of 17p13. The relative level of p53 mRNA expression was examined by Northern analysis, with one tumor showing negligible expression of p53 mRNA. The complementary DNA of p53 was generated from the three tumors showing detectable mRNA expression, and the region between codons 70 and 319 was amplified by the polymerase chain reaction and sequenced. DNA single-base substitutions were detected in two of the tumor cell lines, each resulting in amino acid substitutions. One tumor had an arginine to histidine substitution at position 175, and one tumor had a glycine to aspartic acid substitution at position 245. The observed mutations took place in regions of high cross-species sequence homology, indicating that these regions may be functionally important. The correlation of chromosomal loss in 17p on the cytogenetic and molecular level along with p53 mRNA expression and DNA sequence data indicate that genetic alterations in p53 could be a feature of malignant mesotheliomas and may reveal an important role of asbestos fibers in tumor suppressor gene inactivation.

Blotting, Northern↗

PubMed1991

MYC rearrangement and translocations involving band 8q24 in diffuse large cell lymphomas.

The configuration of the MYC gene in diffuse large cell lymphomas (DLCL) with translocations involving band 8q24 [t(8q24)] has not been systematically studied. We collected cytogenetic and clinical data on 171 consecutive cases of DLCL, including cleaved, noncleaved, and immunoblastic types, of which 96 had DNA available and 124 had abnormal karyotypes. The cases with DNA available were evaluated for MYC rearrangement (MYC-R) by Southern hybridization of EcoRI-digested tumor DNA using an exon-1 probe, a combination of probe and enzyme known to detect over 85% of breaks in sporadic Burkitt's lymphoma. In cases studied at diagnosis, MYC-R, t(8;14)(q24;q32), or other t(8q24) were not prognostically significant. Among the 124 cases with karyotypic abnormalities, seropositivity for human immunodeficiency virus was significantly more common in cases with a t(8q24) (72%) than in cases without it (9%) (P less than .05). Of the four cases with an MYC -R, two had a t(8;14), one had a t(7;8;14)(p15;q24;q32), and one had a t(8;?)(q24;?) and a del(8)(q24). In the three previous cases with translocations involving 8q24 and 14q32, comigration of the rearranged MYC band with either the J region or the switch-mu region of the Ig heavy chain gene could not be demonstrated, leaving the 14q32 breakpoint undefined at the molecular level. Among the remaining 72 cases where both an abnormal karyotype and molecular data were available, 11 had a t(8q24), either t(8;14) or t(8;22)(q24;q11), in the absence of an MYC-R. In these cases, the 8q24 break was presumably located outside of the EcoRI MYC fragment. All 15 cases with a t(8q24) were also screened for point mutations in the PvuII site in the first exon of MYC; two cases that were not MYC-R showed loss of this restriction site. These results indicate that in most DLCL with t(8;14) or other t(8q24), the 8q24 breakpoint lies away from the MYC gene; in a minority of these cases, point mutations in regulatory noncoding regions were detected.

Adult↗

PubMed1991

Histopathological, cytogenetic, and molecular characterization of renal cortical tumors.

We used cytogenetic and restriction fragment length polymorphism (RFLP) analysis methods to define genetic alterations and also correlate the changes with histopathology in renal cortical tumors. The study series is comprised of 50 renal tumors in 4 histological categories: (a) clear cell, nonpapillary, renal cell carcinoma (RCC) (n = 32); (b) nonclear cell, nonpapillary RCC (n = 10); (c) papillary RCC (n = 3); and (d) oncocytic tumors (n = 5). Successful karyotypes were obtained from 28 tumors (56%), of which 17 (61%) were abnormal. Abnormalities of chromosome 3p were seen in 9 tumors, which included unbalanced translocations and terminal or interstitial deletions. Abnormalities of chromosome 5 were identified in 11 tumors, 8 of which were due to unbalanced translocations between 3p and 5q, resulting in an extra copy for the region 5q22----ter. In addition, trisomy or tetrasomy of chromosome 17 was seen in 6 (5 with normal chromosome 3 and one with 3p deletion), trisomy or more copies of chromosome 7 in 8 (4 with 3p deletion, 2 with trisomy or tetrasomy 17, and 2 with trisomy alone), and trisomy 12 in 3 (all with trisomy 17) tumors. Furthermore, relative deficiency of chromosome 17p was seen in 3 (all with deletion 3p) and chromosome 18 in 4 (all with deletion 3p) tumors. RFLP analysis with four chromosome 3 specific probes detected 3p deletions in 19 tumors with the most common breakpoint located between 3p14-21. The 19 3p deletions detected by RFLP included tumors that also showed rearrangement of 3p by cytogenetics (n = 4) and those that showed normal karyotypes (n = 3) in addition to cytogenetic failures (n = 12). Deletions of 17p were seen in 5 of 31 informative cases. Thus, deletions of 3p were seen in a total of 24 tumors by cytogenetic and/or RFLP analysis, 21 of which were clear cell, nonpapillary RCC, whereas 3 had a minor clear-cell component. Oncocytic and nonclear, nonpapillary tumors, on the other hand, did not demonstrate 3p deletions by either technique, whereas trisomy 17 was seen in 3 of the 3 papillary tumors. The loss of alleles from chromosome 17p and 18 and an increased dosage of gene or genes on chromosomes 5q and 7 as seen in high-stage tumors of various histological subtypes may be associated with progression of disease.

Adult↗

PubMed1991

Cytogenetic analysis of 434 consecutively ascertained specimens of non-Hodgkin's lymphoma: correlations between recurrent aberrations, histology, and exposure to cytotoxic treatment.

Cytogenetic abnormalities in non-Hodgkin's Lymphoma (NHL) provide a model system for the analysis of the role of multiple genomic aberrations in human malignancy. In order to define correlations with histology, tumor evolution, and the effects of genotoxic exposure, cytogenetic analysis was performed on 434 specimens of NHL derived from 423 patients consecutively ascertained over a 5-year period (1984-1989). Six recurring translocations (RT) were observed: t(14;18)(q32;q21), t(8;14)(q24;q32), t(11;14)(q13;q32), t(3;22)(q27;11), t(2;5)(p23;q35), and t(1;6)(q21;q25). No translocation was specific to a single histologic subtype. Other structural chromosome abnormalities were analyzed according to break site; groups of related breaks were considered together for statistical analysis. Recurring other structural and numerical aberrations (ROA) encountered in greater than 10% of specimens included rearrangements with breaks at bands 1p32-36, 1q21-23, 6q21-25, and trisomies of chromosomes 7 and 12. ROA with one of these breaks or numerical abnormalities were the sole abnormalities in at least two cases. Correlations were observed among ROA and between ROA and histologic subtypes. Trisomy 7, breaks at 1q21-23, 1p32-36, 6q21-25, and 7q32 were associated with t(14;18); trisomy 18 was associated with trisomy 3; and structural abnormalities of chromosome 17 were associated with breaks at 1p32-36 and 6q21-25. Trisomy 7 and trisomy 12 were more frequent in t(14;18)-bearing intermediate to high grade tumors compared to low grade tumors. Trisomy 12 and breaks at band 1p22 were associated with large cell diffuse lymphomas. Incidence rates of reciprocal translocations, ROA, and measures of karyotypic complexity, including number of breakpoints and marker chromosomes were compared in pretreatment and posttreatment samples. Karyotypic complexity was greater in the posttreatment samples, reflecting an increased frequency of nonrecurring and low incidence aberrations. These results better define the association of genomic aberrations and tumorigenesis, histologic transformation, and tumor progression.

Alkylating Agents↗

PubMed1991

Clonal cytogenetic abnormalities in Hodgkin's disease.

Cytogenetic studies of Hodgkin's disease (HD), in contrast to those of non-Hodgkin's lymphoma (NHL), have been limited to small numbers of cases with infrequently recurring aberrations, underscoring the need for additional studies in establishing a coherent cytogenetic picture of HD. Over a 6 1/2-year period, we received 95 specimens of HD for cytogenetic analysis. Analyzable chromosome preparations were obtained in 70 cases, of which 57 (81%) showed only normal metaphases. In the remaining 13 cases (19%), karyotypic abnormalities were observed that were nonclonal in 3 and clonal in 10. The latter 10 cases included 6 of the nodular sclerosis subtype, 3 mixed cellularity, and 1 lymphocyte-depleted; 8 of the specimens were obtained pretreatment and 2 posttreatment. Two of the cases had a clonal numerical aberration, monosomy 17 in one and trisomy 13 in the other, as their sole abnormality. The remaining 8 cases showed complex karyotypes with multiple structural rearrangements; in 3 of these, the abnormal clone was near-tetraploid. Bands involved more than once included 1p36, 1q21, and 4q35, each in 2 cases. Arms involved more than once included 6q (6q13,6q23), 9p (9p13,9p21), and 5q (5q15,5q35). Three patients had loss of part or all of 6q (del(6)(q13),del(6)(q23),i(6p). Bands 14q32 and 18q21 were not involved in any case, contrary to some previous reports. Our results confirm the frequent occurrence of 1p, 1q, and 6q abnormalities in HD. In addition, we have identified a 5q35 breakpoint, which has recently been shown to be highly specific for Ki-1-positive NHL in a case of typical nodular sclerosis HD. Its presence in HD may represent a cytogenetic link between the two entities, which are immunophenotypically related but clinically and histologically distinct.

Aneuploidy↗

PubMed1991

Transformation of human kidney proximal tubule cells by a src-containing retrovirus.

Analysis of the cell-surface antigenic phenotypes of normal and malignant renal cells demonstrates that approximately 90% of cultured normal human kidney cells and virtually all renal cell carcinomas (RCC) derive from the proximal tubule (PT) cell of the nephron. In the present study, the v-src oncogene was introduced into cultured normal human PT cells, and the effects of the v-src-encoded protein (pp60v-src) on the biologic and genetic phenotype of these cells were determined. V-src-containing PT cells underwent a series of phenotypic changes characteristic of renal cells in vivo. These included (i) alterations in morphology, (ii) an increase in proliferative capacity, (iii) loss of contact inhibition, (iv) immortalization and (v) tumorigenicity. Moreover, v-src-infected PT cells developed non-random clonal karyo-typic abnormalities which are commonly observed in RCCs, including a deletion of chromosomal region 3p14-21, one of the most frequent deletions observed in human renal tumors. These results indicate that pp60v-src can initiate a complex process leading to the transformation of PT cells. This process includes the induction of genetic instability. Finally, these data provide experimental evidence corroborating cytogenetic and molecular data that a deletion of genes on chromosome 3p is a critical event in the transformation of the human renal cell.

Animals↗

PubMed1990

11p13-15 is a specific region of chromosomal rearrangement in gastric and esophageal adenocarcinomas.

In a cytogenetic analysis of 9 gastric and lower esophageal adenocarcinomas, we detected nonrandom rearrangements involving the region 11p13-15 in 8, thus identifying for the first time a specific chromosomal lesion in these tumors. In addition, rearrangements involving 3p21, translocations among the D group chromosomes, and i(5p) were each observed in more than half of the cases. The overall pattern of aberrations encountered in adenocarcinomas of gastric and lower esophageal origin was similar, suggesting that the tumors arising at these anatomical sites are biologically related. We also encountered cytogenetic evidence for gene amplification in the form of homogeneously staining regions and double-minute chromosomes in primary as well as metastatic lesions, which is consistent with amplification of a number of cellular oncogenes in these tumors detected by others and us at the molecular level. These cytogenetic findings are discussed in relation to nonrandom chromosome abnormalities and gene amplification reported in other types of adenocarcinoma.

Adenocarcinoma↗

PubMed1990

Cytogenetic analysis of chimerism and leukemia relapse in chronic myelogenous leukemia patients after T cell-depleted bone marrow transplantation.

Serial cytogenetic studies were performed on 64 patients with chronic myelogenous leukemia (CML) after T cell-depleted allogeneic bone marrow transplantation (BMT). Forty patients with CML in chronic phase (CP) received cytoreduction followed by BMT with HLA-matched T cell-depleted allogeneic marrow. The remaining 24 patients were transplanted in second chronic, accelerated, or blastic phase, or received T cell-depleted grafts with a dose of T cells added back. The Y chromosome and autosomal heteromorphisms were used to distinguish between donor and host cells. Mixed hematopoietic chimerism (presence of donor and host cells) was identified in 90% of patients in first CP. The Philadelphia (Ph) chromosome reappeared in 16 of the 40 first CP CML patients. As expected, patients who had detectable Ph chromosome positive cells at any time during the posttransplant period had a high likelihood of subsequent clinical relapse. Transient disappearance of the Ph positive clone was rarely observed, and was followed by reappearance of the Ph chromosome or clinical relapse. A subset of engrafted patients with greater than 25% host cells within 3 months post-BMT had a significantly shorter survival time free of cytogenetic or clinical relapse compared with other patients. In patients who had received donor T cells added to the T cell-depleted graft, there was a higher proportion of complete chimerism. Clonal progression of Ph positive as well as negative cells was observed and may be the result of radiation induced breakage. Serial cytogenetic studies of patients post-BMT can provide useful information regarding the biologic and clinical behavior of CML.

Adult↗

PubMed1990

Cytogenetic and immunohistochemical evidence for the germ cell origin of a subset of acute leukemias associated with mediastinal germ cell tumors.

Most acute leukemias occurring in patients with mediastinal germ cell tumors (MGCTs) appear to be primary rather than therapy-related; however, no data have been obtained to date to confirm the hypothesized germ cell origin of the leukemias in this syndrome. We identified six male patients with this syndrome treated at Memorial Sloan-Kettering Cancer Center: in all six, the leukemia was studied immunohistochemically for various hematologic and germ cell antigens; in four, the karyotype of the leukemia was available; in one, the MGCT had also been karyotyped. In three patients, we found evidence of a germ cell origin of the acute leukemias. A 19-year-old male developed an acute myeloblastic leukemia 11 months after presenting with an MGCT; karyotypes of the two tumors showed them to be clonally related, both showing an i(12p), a cytogenetic marker of germ cell tumors. A 16-year-old male with probable Klinefelter's syndrome presented simultaneously with acute monocytic leukemia and an MGCT; although the MGCT was not karyotyped, the leukemia showed an i(12p). A 23-year-old male developed concurrently an MGCT and acute myelomonocytic leukemia; the leukemia cells coexpressed myelomonocytic antigens (HAM56, My4, My9) and cytokeratin, suggesting dual differentiation, myeloid and germ cell. Evidence for a germ cell origin of the acute leukemias in the three other patients was not obtained, although in all three the MGCT and the leukemia occurred simultaneously, supporting an etiologic relationship. Hence, these leukemias may represent another form of non-germ cell malignancy developing in germ cell tumors. All patients died of the leukemia, with a median survival of less than 2 months. This syndrome may be a useful pathologic model for the study of germ cell differentiation and hematopoietic ontogeny.

Adolescent↗

PubMed1990

Immunohistochemical, molecular, and cytogenetic analysis of a consecutive series of 20 peripheral T-cell lymphomas and lymphomas of uncertain lineage, including 12 Ki-1 positive lymphomas.

Although several independent series of non-Hodgkin's lymphomas (NHLs) have been subjected to cytogenetic studies or analyses of lineages by assaying for clonal immunophenotypes and clonal rearrangements affecting immunoglobulin (IG) and T-cell receptor (TCR) genes, no published reports exist of series of non-B-cell NHLs on which cytogenetic, immunohistochemical, and IG and TCR gene rearrangement studies have been undertaken together. Among 343 NHLs ascertained prospectively between January 1984 and December 1988 at the Memorial Sloan-Kettering Cancer Center, 278 cases with clonal chromosome abnormalities were identified. Of the latter, 20 were non-B-cell NHLs, which in turn comprised 15 peripheral T-cell lymphomas (PTCLs) and 5 lymphomas of uncertain lineage (LULs). The LULs either were biogenotypic, had discordant immunophenotype and immunogenotype, or showed no evidence of B-cell, T-cell, or histiocytic derivation. Of the 15 PTCLs, eight expressed the Ki-1 antigen and four of these had translocations involving the band 5q35 [t(5q35)]. Of the five LULs, four expressed the Ki-1 antigen and one of these had a translocation involving band 5q35. Previous studies have associated t(5q35) with Ki-1 positive NHLs characterized histologically by a pleomorphic diffuse large cell morphology. In our series of 12 Ki-positive non-B-cell NHLs, five (42%) had a 5q35 translocation. They were histologically indistinguishable from the subset without the translocation. The frequent lineage uncertainty exhibited by Ki-1 positive NHLs of similar histology and cytogenetic abnormalities suggests their derivation from an early uncommitted lymphoid cells.

Antigens, Differentiation↗

PubMed1990

Neural differentiation in small round cell tumors of bone and soft tissue with the translocation t(11;22)(q24;q12): an immunohistochemical study of 11 cases.

Clinical, cytogenetic, histopathologic, and immunohistochemical data were obtained in a series of 11 small round cell tumors (SRCT) of bone and soft tissue with the translocation t(11;22) (q24;q12). Ten cases were primary in bone, and one was of extraskeletal origin. According to conventional histopathologic criteria, 10 cases were Ewing's sarcomas (ES) and one was a peripheral neuroectodermal tumor (PNET). Besides the t(11;22), six cases had additional chromosomal aberrations, including trisomy 7 and partial trisomy for the long arm of chromosome 1, which have both been described as nonspecific secondary abnormalities often associated with tumor progression. The tumors were screened for neural differentiation with an antibody panel consisting of neuron-specific enolase, S100 protein, Leu-7, chromogranin, synaptophysin, and neurofilament. Three cases of ES were positive for S100 protein. The PNET and one case of ES were positive for neuron-specific enolase. All of the remaining immunohistochemical stains were negative. Hence, five of 11 SRCT of bone or soft tissue with the t(11;22) showed morphologic and/or immunohistochemical evidence of neural differentiation. In this limited series of cases, no cytogenetic or prognostic differences could be demonstrated between cases with and without a neural phenotype. Our results support the hypothesis that SRCT of bone of soft tissue with the t(11;22) form a single biologic entity displaying varying degrees of neuroectodermal differentiation. The clinical significance of additional cytogenetic abnormalities and of morphologic or immunohistochemical evidence of neural differentiation in this group of tumors needs to be further studied.

Adolescent↗

PubMed1990

Immunoglobulin heavy chain and alpha T-cell receptor genes rearrange in T-cell leukemia associated with a t(14;14) (q11.2;q32) translocation.

We report here a cytogenetic and molecular analysis of two cases of T-cell leukemia with t(14;14) (q11.2;q32). Through in situ hybridization and Southern blotting, using radioactively labeled immunoglobulin heavy chain (IGH) and alpha T-cell receptor (TCRA) gene probes, we found in both tumors that the loci of both IGH and TCRA were rearranged. Molecular analysis of the t(14;14) clearly demonstrated that in some tumors rearrangements of the IGH and TCRA genes are associated with interchromosomal exchanges that result in specific chromosome translocations that confer a proliferative advantage and predisposition to leukemic transformation. The implication of these rearrangements for normal and neoplastic T-cell development is discussed.

Blotting, Southern↗

PubMed1989

Leukemic differentiation of a mediastinal germ cell tumor.

The biological basis for acute leukemia associated with mediastinal germ cell tumors has remained unexplained due to lack of critical data that would illuminate the genetic relationship between the two tumors in a given patient. Here we present results of serial cytogenetic investigations on the pretreatment and posttreatment mediastinal yolk sac tumor and immature teratoma biopsies and two separate leukemic bone marrow aspirates from a patient who developed acute nonlymphocytic leukemia 11 months after the initial diagnosis of the germ cell tumor. Presence of an i(12p) in all tumor clones and trisomy 21 in one clone in the posttreatment mediastinal tumor and all leukemic clones establishes the common origin of all tumor clones and shows that in this case the leukemia was derived from the malignant germ cell clone.

Adult↗

PubMed1989

Nonrandom chromosomal aberrations are associated with sites of tissue involvement in non-Hodgkin's lymphoma.

In an effort to assess the utility of pretreatment cytogenetics as indicators of sites of involvement by lymphoma, clinical and cytogenetic correlations were performed on 133 consecutive specimens derived from 130 patients with non-Hodgkin's lymphoma. Nonrandom chromosomal aberrations detected at the time of diagnosis were associated with sites of clinical involvement presenting initially or during the progression of the lymphoma. Statistically significant associations included translocation breaks involving the chromosomal region 1p32-36 and bone marrow involvement, chromosome 14 abnormalities including breaks at 14q22-24 and splenic involvement, chromosome 9 abnormalities and pulmonary involvement, and monosomy 11 and bone involvement. A significant correlation was also observed between breaks involving the region 6q22-24, detected during the course of disease, and bone marrow involvement by lymphoma. The relationship of the sites of nonrandom chromosomal breakage reported here to known cellular oncogenes and implications to concepts of tumor evolution and spread are discussed.

Bone Marrow↗

PubMed1989

Detection of posttransplant minimal disease chronic myelogenous leukemia by bcr rearrangement analysis.

Until recently, cytogenetic detection of the Philadelphia chromosome (Ph) was the only reliable test to diagnose chronic myelogenous leukemia (CML) and detect minimal disease or early relapse following treatment. However, the recently developed ability to detect the Ph chromosome as a rearrangement in the bcr gene of chromosome 22 permits identification of the leukemic clone comprising as little as 5% of the cell population. We present results of simultaneous cytogenetic and DNA rearrangement studies in 28 CML patients considered for or treated with bone marrow transplantation. Our results show that the molecular method is significantly more sensitive than the cytogenetic method in the detection of minimal disease Ph-positive clones.

Bone Marrow Transplantation↗

PubMed1989

Cytogenetic and molecular genetic analysis of abnormal cells in Hodgkin's disease.

Eleven tumors from ten patients with Hodgkin's diseases (HD) were characterized by histologic, cytogenetic, immunophenotypic, and genotypic studies. Cell surface markers for lymphocyte antigens did not show clonal excess. Five tumors showed the presence of karyotypically abnormal cells, but no common abnormalities were found. The remaining six tumors showed normal karyotypes. Ten tumors were analyzed for gene rearrangements with probes for IgJH, IgCk. IgC lambda, and TCR-beta genes. The IgJH probe detected a minor clonal population (about 5%) in one tumor with abnormal karyotype; three tumors with abnormal karyotypes showed germline genotype. In contrast, four of the six tumors with normal karyotypes showed rearrangements in IgJH (one tumor) and in C-lambda (three tumors) genes. The pattern of gene rearrangement observed in these tumors did not obey the hierarchy described in B-cell differentiation. These results suggest that B-cell lineage cannot be attributed unequivocally to the clonal populations in HD.

Adolescent↗

PubMed1989

18q21 rearrangement in diffuse large cell lymphoma: incidence and clinical significance.

Cytogenetic, molecular genetic and clinical information was collected for 102 cases of diffuse large cell lymphoma (DLCL) ascertained in a diagnostic laboratory over a 3-year period. Nineteen cases showed evidence of either a t(14;18) or a rearrangement of one of three genomic probes for breakpoints at 18q21. Clinical and histologic evidence of transformation from follicular lymphoma or chronic lymphocytic leukaemia was available in six cases. Except for age, prognostic clinical variables (LDH, stage, extranodal involvement) were similar between the 18q21 rearranged patients and DLCL patients without 18q21 rearrangement. At a median follow-up in excess of 2 years for both groups, there was no difference in overall survival between the 18q21 rearranged group compared to DLCL patients lacking this genetic abnormality. The median disease-free survival for the 18q21 rearranged group, however, was significantly shorter and survival in partial remission longer. The propensity for extended survival of the 18q21 rearranged DLCL patients with residual or recurrent disease resembled the clinical behaviour of nodular lymphoma patients with t(14;18). These results suggest that cytogenic or molecular genetic identification of a chromosome 18q21 translocation may be of prognostic significance in the analysis of treatment protocols for patients with DLCL.

Adult↗