Genetic analysis as an aid in diagnosis for patients with midline carcinomas of uncertain histologies.

The tumors of nine patients with carcinomas of uncertain histogenesis (eight with poorly differentiated carcinomas involving primarily midline structures and one with a diagnosis of seminoma and atypical clinical features) were studied by cytogenetic and Southern blot analyses. Four of the eight patients with poorly differentiated carcinomas had abnormalities of chromosome 12 consistent with a diagnosis of germ cell tumor. These abnormalities comprised an i(12p) in two patients and a del(12q) in a third patient detected by cytogenetic analysis and multiple copies of 12p detected by Southern blot analysis in a fourth patient. Three of these four patients with a diagnosis of germ cell tumor established by genetic analysis achieved a complete response to cisplatin-based chemotherapy. The tumor biopsy of one patient showed a t(11;22) (q24;q12), and this patient had chemotherapy directed to neuroepithelioma. Cytogenetic analysis was unsuccessful for the tumors of three patients; these tumors did not have multiple copies of 12p detected by Southern blot analysis. These patients did not respond to cisplatin-based chemotherapy. One patient with a diagnosis of extragonadal seminoma failed to respond to cisplatin-based chemotherapy and had a second tumor biopsy performed that demonstrated a t(8;14) (q24;q32). This patient's diagnosis was changed to a non-Hodgkin's lymphoma. Thus, genetic analysis provided a diagnosis in six of nine patients. Cytogenetic and molecular analyses are useful clinical tools for the determination of histogenesis in some patients with poorly differentiated carcinomas of uncertain histology.

Abnormalities of chromosome 16 in association with acute myelomonocytic leukemia and dysplastic bone marrow eosinophils.

Six patients with M4 acute myelomonocytic leukemia ( AMMoL ) were identified who had abnormalities of chromosome 16 in bone marrow cells. Five had a pericentric inversion, inv(16)( p13q22 ), and a sixth patient had a translocation, t(16;16)(p13.1;q22). Each of these six patients had bone marrow eosinophils that were abnormal in morphology on light and/or electron microscopy and by cytochemical stains. The eosinophils constituted 1%-24% of nucleated marrow cells. Of 61 acute nonlymphocytic leukemia (ANLL) patients, all those with AMMoL and abnormal bone marrow eosinophils had an inv(16) or a t(16;16). One other patient in this group had a rearrangement of chromosome 16 (with a break in the short arm at band p13); however, the ANLL type was M1 and no abnormal eosinophils were present. Four patients with ANLL types other than M4 had an increase in marrow eosinophils; three in whom the eosinophils appeared normal and one with ANLL-M2 and bizarre eosinophils morphologically distinct from those seen in AMMoL . Chromosome pair 16 was normal in the latter four patients. AMMoL with dysplastic bone marrow eosinophils appears to represent a unique clinicopathologic entity associated with several related abnormalities affecting 16q . The morphologic features of both blasts and eosinophils may be more important than the absolute number of eosinophils in the marrow in identifying this group of patients. This may have prognostic importance as five of six patients achieved complete remission with standard antileukemic therapy and are still alive.

In vitro establishment of AIDS-related lymphoma cell lines: phenotypic characterization, oncogene and tumor suppressor gene lesions, and heterogeneity in Epstein-Barr virus infection.

Lymphoma represents a major source of morbidity and mortality among AIDS patients. AIDS-associated non-Hodgkin lymphomas (AIDS-NHL) are almost invariably B-cell derived, are classified as high or intermediate grade lymphomas, and display three main histologic types: namely, small non-cleaved cell lymphoma (SNCCL), large cell immunoblastic plasmacytoid lymphoma (LC-IBPL), and large cell lymphoma (LCL). Here we report the in vitro establishment of three new AIDS-NHL cell lines (termed HBL-1, HBL-2, and HBL-3) derived from three AIDS-SNCCL patients differing in primary tumor sites and risk factors for HIV infection. The derivation of the cell lines from the original tumor clones was established by immunophenotypic and molecular genetic analysis. These cell lines display clonal immunoglobulin gene rearrangement, express surface immunoglobulin and B-cell restricted markers, and exhibit a phenotype consistent with SNCCL. Monoclonal Epstein-Barr virus infection was found in only one of the cell lines (HBL-1). Cytogenetic analysis demonstrated the presence of a chromosomal translocation involving the c-myc proto-oncogene and an immunoglobulin locus in all three cell lines. The pattern of genetic lesions detected in HBL-1, HBL-2, and HBL-3 reflects that found in primary AIDS-SNCCL and includes activation of the c-myc oncogene as well as inactivation of the p53 tumor suppressor gene. These cell lines should prove useful in studies of the biological, immunological, and viral factors involved in AIDS-associated lymphomagenesis.

Detection of gains and losses in 18 meningiomas by comparative genomic hybridization.

Comparative genomic hybridization (CGH) was used to examine gains and losses in 18 meningioma tumors that had been previously analyzed for loss of heterozygosity (LOH) at 22q12. Partial or complete losses were seen by CGH in only 9 of 18 cases on chromosome 22. This compares with 11 of 18 losses of single or more loci by LOH. The discrepancy in these results in probably explained by the increased sensitivity of LOH by using microsatellite markers that are able to detect small deletions, whereas losses on the order of 10-15 megabases are required for confident identification by CGH. There was no consistent pattern of gains or losses by CGH, including those tumors that lacked LOH at 22q12. In one tumor of interest in which CGH and LOH studies failed to demonstrate loss on chromosome 22, CGH identified an area of amplification at 17q22-23.

BCL6 gene rearrangement and other cytogenetic abnormalities in diffuse large cell lymphoma.

Evidence for rearrangement of the BCL6 gene at 3q27 has been documented in 20-30% diffuse lymphomas with a large cell component (DLLC), and was found to be of prognostic significance at the time of diagnosis. To incorporate these observations into current cytogenetic and clinical prognostic models, 76 cases of DLLC with known BCL6 status were analyzed. Cytogenetic indicators of progression, including trisomy 7, trisomy 12, del(6)(q21q25), and structural alterations of 17p were less frequent in BCL6 rearranged DLLC compared to BCL6 germline tumors. Despite a 93% overall survival at median follow-up of 30 months, a trend for continued relapse resulted in a projected freedom from progression for the BCL6 rearranged cohort of 66% at 4 years, compared to 39% for the BCL6 germline cohort. Six cases among the BCL6 rearranged group lacked additional cytogenetic indicators of progression and remained free of disease at follow-up in excess of 7 years, whereas BCL6 rearranged cases with increasing numbers of cytogenetic aberrations showed decreased intervals free from progression of disease. These results suggest that BCL6 rearrangement should be combined with other known clinical and cytogenetic indicators in prognostic analyses of patients with DLLC.

Determination of sex chromosomal constitution and chromosomal origin of drumsticks, drumstick-like structures, and other nuclear bodies in human blood cells at interphase by fluorescence in situ hybridization.

The sex chromosomal constitution has been determined in various types of human leukocytes at interphase by use of fluorescence in situ hybridization with X- and/or Y-specific DNA probes. It is found that during aging and differentiation of myelocytes into polymorphs there is no significant change in the relative frequency of various types of male and female cells with a specific type of sex chromosomal constitution. Non-random variability of the relative proximity between the X chromosomes within the nuclei is also observed in female cells. Moreover, we are the first to determine that sex-specific "drumsticks" and "sessile nodules" in female polymorphs originate from the X chromosomes and that non-sex-specific "drumstick-like" bodies in male polymorphs are of Y chromosomal origin.

Del (7)(q32) is associated with a subset of small lymphocytic lymphoma with plasmacytoid features.

Deletions of the long arm of chromosome 7, previously documented in myelodysplasias and myeloid leukemias, have also been noted in lymphoid malignancies. Of 558 karyotypically abnormal specimens of non-Hodgkin's lymphoma (NHL) serially ascertained over an 8-year period, del(7q) was identified in 24 cases, 10 of which were of the small lymphocytic (sm lym) subtype. Del(7q) was the third most common karyotypic abnormality among the cohort of 61 sm lym cases in this ascertainment. Mapping of the deletions identified a region of common deletion affecting 7q32, which was the sole karyotypic abnormality in 2 cases. Eight of the ten sm lym cases were characterized by plasmacytoid features in histologic sections of lymphoma tumors or circulating cells in the peripheral blood. The del(7)(q32) was accompanied by 14q32-associated translocations in 11 of the 14 cases with histologies other than sm lym, compared with 2 of the sm lym cases. Extranodal involvement was more frequent in the del(7)(q32) sm lym NHLs, although median survival was typical of other low-grade lymphomas. These results suggest that loss or inactivation of a putative tumor-supressor gene at 7q32 may play a role the progression of lymphomas as well as constitute an early event in the pathogenesis of lymphoplasmacytoid tumors.

Gene amplification in non-Hodgkin's lymphoma.

Among 426 consecutively ascertained and karyotypically abnormal non-Hodgkin's lymphoma (NHL) tumours, cytological evidence for gene amplification in the form of homogeneously staining regions (HSRs) was encountered in nine cases of large cell diffuse lymphoma (LC-DL). The mean age of patients with HSRs was 62.9 years and four died within a year of diagnosis. To identify candidate gene(s) amplified in these tumours, we performed a Southern blot analysis of tumour DNA using probes for 23 known protooncogenes and the multidrug resistance gene, PGY1. Besides a two-fold amplification of the BCL2 gene in two cases, no evidence for overt amplification of any of the genes assayed was found. To confirm DNA amplification in these specimens we performed the DNA in-gel renaturation assay. Evidence for presence of amplified DNA fragments was obtained in four of seven specimens. These results suggest amplification of a novel gene(s). To our knowledge, this is the first formal study of gene amplification in a large consecutively ascertained series of fresh lymphoma biopsies.

High molecular weight DNA from fixed cytogenetic preparations.

Cell pellets that have been stored in routine clinical cytogenetic fixative were studied for the presence of intact DNA. A method for the isolation of high molecular weight DNA from fixed cytogenetic preparations of human leukocytes, bone marrow, and cell hybrid cultures is presented. DNA preparations from fixed pellets were cleaved with restriction enzymes, transferred to nitrocellulose filters after agarose gel electrophoresis, and hybridized to radiolabeled probes to demonstrate that fixed cell pellets could yield DNA of sufficient quality for Southern blot hybridization analysis. This protocol may be useful for molecular analysis of DNA from fixed cell pellets of patients who are unavailable for additional sampling.

Induction of terminal differentiation and nuclear appendage(s) formation in a human myeloid leukaemia cell line (HL-60).

In vitro terminal differentiation in a female myeloid leukaemia cell line (HL-60) was induced by either of the two inducing agents, dimethylsulphoxide (DMSO) and dimethylformamide (DMF). A higher frequency of more mature myeloid cells was noted with increasing concentrations of the inducing agents up to the optimal dose limits for cell viability, and with longer post-induction incubation periods. The highest percentage of polymorphs was obtained at 8 days post-induction with 1.25% DMSO and after 6 and 8 days exposure to 90 mM DMF. A proportion of polymorphs showed non-sex specific drumstick-like nuclear appendages, which were morphologically similar to the sex-specific drumsticks found in polymorphs from normal females in vivo. The correlation between the nuclear lobe counts and the frequencies of drumstick-like appendages in polymorphs was also similar to that reported for drumsticks in blood cells in vivo. The various stages of terminal differentiation and nuclear appendage formation in polymorphs under induced differentiation were similar to those occurring in vivo. Chromosomal analyses of this cell line indicated that individual cells had lost one X chromosome, and no portion of the missing X was detected in any of the rearranged chromosomes. Since no truly sex-specific drumsticks appeared to be present in the polymorphs of this cell line containing only one X chromosome, the study supports the accepted notion that there is a correlation between drumstick frequency and the presence of one versus two X chromosomes.

Localization of the proto-oncogene MOS to 8q11-q12 by in situ chromosomal hybridization.

The human MOS proto-oncogene has been mapped previously to two different sites on chromosome 8 (8q22 and 8q11). Here we report in situ hybridization data from two different laboratories which confirm the localization of MOS to the proximal region of the long arm of chromosome 8, at 8q11-q12.

The AKT1 proto-oncogene maps to human chromosome 14, band q32.

The human AKT1 gene is the proto-oncogene of the viral oncogene v-akt. The AKT1 gene has been localized to human chromosome 14, band q32, proximal to the heavy-chain immunoglobulin locus (IGHM), by analysis of human-hamster somatic cell hybrids and by in situ hybridization. Chromosome rearrangements of this band which occur in T-lymphoid malignancies and Hodgkin's disease may affect the AKT1 gene.

t(9;14)(p13;q32) denotes a subset of low-grade non-Hodgkin's lymphoma with plasmacytoid differentiation.

In this series of 426 consecutively ascertained, karyotypically abnormal non-Hodgkin's lymphomas (NHLs) derived from 407 patients, a t(9;14)(p13;q32) was encountered in 7 cases; an additional case demonstrated t(9;14)(p1?3;q32). At the time of detection of t(9;14), four cases were small lymphocytic lymphomas with plasmacytoid features; in three of these the t(9;14) was the sole karyotypic abnormality. In two cases of large-cell NHL demonstrating t(9;14), retrospective review of prior lymph node biopsies showed the presence of a small lymphocytic lymphoma of the plasmacytoid subtype. The remaining two cases comprised a large-cell lymphoma of the brain and a follicular NHL. Thus, six of eight cases (75%) had an initial identical low-grade histology. Immunohistochemical analysis of six cases showed no reactivity with CD1, CD2, CD4, CD5, CD8, and CD10 and high reactivity with CD19 and CD20. All four lymphocytic lymphomas and one of the two large-cell NHLs showed cytoplasmic Ig, consistent with plasmacytoid differentiation. Of the eight cases in this series, six presented with or developed stage IV disease; all were characterized by a 6-month to 5-year clinical phase of indolent disease before treatment was instituted. All five patients with low-grade NHL at the time of cytogenetic analysis were alive with recurrent disease at 3-year median follow-up. The remaining three patients with large-cell diffuse histologies relapsed after intensive therapy and expired at a median of 3 years from diagnosis; two of these showed previous or metachronous small lymphocytic tumors. These results suggest a novel biologically distinct subset of NHL; a neoplasm of mature B lymphocytes with plasmacytoid differentiation, characterized by t(9;14); and an indolent presentation followed by gradual clinical progression of disease.

Clinical and morphologic features of B-cell small lymphocytic lymphoma with del(6)(q21q23).

Deletions of the long arm of chromosome 6 have been described in acute and chronic lymphocytic leukemia (ALL and CLL) and prolymphocytic leukemia (PLL), and have been associated with t(14;18)(q32;q21) in non-Hodgkin's lymphoma (NHL). Of 55 cases of small lymphocytic (sm lym) NHL, deletions of 6(q21q23) were the most common recurring cytogenetic abnormality. Among 14 sm lym NHL with del(6)(q21q23), this abnormality occurred as a solitary change in 3 cases. Each of these 3 cases, and 5 additional cases with del(6q) and other abnormalities, showed atypical larger forms with the morphologic appearance of prolymphocytes or paraimmunoblasts in the peripheral blood. In comparison, of the 11 cases without del(6q) and circulating abnormal cells, prolymphocytoid forms were observed in 4 cases (P < .001). Of the 31 sm lym without del(6q), trisomies of chromosomes 3, 12, or 18, or t(11;14)(q13;q32) occurred in greater than 10% of cases. Proliferation centers or infiltration by larger forms were observed in similar proportions of tissue sections derived from sm lym NHL with or without del(6q). The presence of the larger forms in the peripheral blood did not have an adverse prognostic impact on the survival of the del(6q) cohort, who experienced a median survival in excess of 6 years. All 14 cases of del(6q) sm lym NHL were characterized by a mature B-cell phenotype. Expression of CD11c, a feature of a CLL/PLL variant previously described, was not detected in 9 cases analyzed. In 5 cases of del(6q) sm lym NHL, no circulating abnormal lymphocytes were noted. Twelve cases presented with, or developed, clinical splenomegaly. These results suggest that deletion of a gene or genes at 6q21-23 is associated with the pathogenesis of a subset of B-cell sm lym NHL that may display larger prolymphocytoid cells in the peripheral blood, but that follows a clinical course typical of other well-differentiated lymphocytic neoplasms.

p53 overexpression as a marker of poor prognosis in mantle cell lymphomas with t(11;14)(q13;q32).

The t(11;14)(q13;q32) translocation, which juxtaposes the BCL1 oncogene with the Ig heavy chain locus, has been associated with an uncommon subtype of non-Hodgkin's lymphoma (NHL) termed mantle cell lymphoma (MCL). To date, no molecular marker that serves as an indicator of tumor progression or clinical prognosis has been described for NHLs with this translocation. We examined a panel of NHLs with t(11;14) for overexpression of p53 and correlated the results with single-strand conformation polymorphism (SSCP) analysis, karyotypic features, and clinical course. NHLs with t(11;14) were identified from 30 patients. The diagnosis was MCL for 23 of 30, small lymphocytic lymphoma for 4 of 30, and diffuse large-cell lymphoma for 3 of 30 cases. The results of immunohistochemistry analysis using a monoclonal anti-p53 antibody on paraffin-embedded specimens were compared with the SSCP data, the tumor karyotypes, and clinical course of each patient. DNA sequencing of exons was performed on cases that showed conformational changes by SSCP analysis. NHLs from 5 of 23 patients with MCL were positive for p53 overexpression. Deletions of chromosome 17p were identified in 2 of 30 cases, both of which were MCLs showing p53 overexpression. Two of the five MCLs with p53 overexpression showed evidence for TP53 mutations. None of the 18 MCLs negative for p53 overexpression showed conformational changes by SSCP. For these 18 patients with MCLs that did not overexpress p53, the median survival was 63 months, compared with 12 months for the 5 patients with MCLs positive for p53 overexpression (P < .001). These results suggest that p53 overexpression in MCL with t(11;14)(q13;q32) may serve as a marker of poor prognosis.

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.

Localization by chromosome microdissection of a recurrent breakpoint region on chromosome 6 in human B-cell lymphoma.

Deletion of the long arm of chromosome 6 (6q) is one of the most common chromosomal alterations in human B-cell lymphomas. Conventional cytogenetic banding analysis and loss-of-heterozygosity (LOH) studies have detected several common regions of deletion ranging across the entire long arm (6q), with no defined recurrent breakpoint yet identified. We describe here a strategy combining chromosome microdissection and fluorescence in situ hybridization (Micro-FISH) to determine a minimal region of deletion along chromosome 6. Seven clinical cases and one cell line of follicular lymphoma containing a t(14;18) and one case of diffuse lymphoma, also with a t(14;18), were used for this study. All nine cases had previously defined abnormalities of chromosome 6 determined by cytogenetic analysis. The results of chromosome dissection were unexpected and in contrast to the suggestion of disparate breakpoints by conventional chromosome banding. Specifically, Micro-FISH analysis provided evidence for a common breakpoint at 6q11 in seven of nine cases. After Micro-FISH analysis, all of the presumed simple deletions of chromosome 6 were carefully reanalyzed and shown to actually represent either nonreciprocal translocations (three cases), interstitial deletions (five cases), or isochromosome (one case). The recurrent proximal breakpoint (6q11) was detected in seven of nine cases, with the minimal region of deletion encompassing 6q11 to 6q21. By analogy to other tumor systems, the identification of recurring breakpoints within 6q11 may suggest that a gene(s) important to the genesis or progression of follicular lymphoma can be localized to this band region.

Molecular cytogenetic analysis of 11 new breast cancer cell lines.

We describe a survey of genetic changes by comparative genomic hybridization (CGH) in 11 human breast cancer cell lines recently established in our laboratory. The most common gains took place at 8q (73%), 1 q (64%), 7q (64%), 3q (45%) and 7p (45%), whereas losses were most frequent at Xp (54%), 8p (45%), 18q (45%) and Xq (45%). Many of the cell lines displayed prominent, localized DNA amplifications by CGH. One-third of these loci affected breast cancer oncogenes, whose amplifications were validated with specific probes: 17q12 (two cell lines with ERBB2 amplifications), 11q13 (two with cyclin-D1), 8p11-p12 (two with FGFR1) and 10q25 (one with FGFR2). Gains and amplifications affecting 8q were the most common genetic alterations in these cell lines with the minimal, common region of involvement at 8q22-q23. No high-level MYC (at 8q24) amplifications were found in any of the cell lines. Two-thirds of the amplification sites took place at loci not associated with established oncogenes, such as 1q41-q43, 7q21-q22, 7q31, 8q23, 9p21-p23, 11p12-p14, 15q12-q14, 16q13-q21, 17q23, 20p11-p12 and 20q13. Several of these locations have not been previously reported and may harbour important genes whose amplification is selected for during cancer development. In summary, this set of breast cancer cell lines displaying prominent DNA amplifications should facilitate discovery and functional analysis of genes and signal transduction pathways contributing to breast cancer development.

Two rearranged MET alleles in MNNG-HOS cells reveal the orientation of MET on chromosome 7 to other markers tightly linked to the cystic fibrosis locus.

We have found that two alleles of the MET locus are rearranged in the human cell line MNNG-HOS. One allele is the previously characterized TPR-MET oncogene and the other is found on a der(7)t(1;7)(q23;q32) marker chromosome. These data and in situ chromosomal hybridization analysis would indicate that MET and, therefore, the cystic fibrosis locus are located at bands q31-q32 on human chromosome 7. Using somatic cell hybrids, we show that the chromosome containing the TPR-MET oncogene is grossly rearranged and contains both the upstream and downstream portions of the MET protooncogene locus. These results demonstrate that the TPR-MET oncogene rearrangement involving chromosomes 1 and 7 is either due to an insertion of TPR sequences into the MET locus or is more complex. We also show that the upstream MET protooncogene locus is deleted on der(7), while the downstream portion is retained. We cannot exclude that this is due to an interstitial chromosomal deletion or to a more complex rearrangement, but if MET maps at the breakpoint in der(7), then the 3' end of the MET transcription unit should be oriented towards the centromere. We also show that other DNA restriction fragment length polymorphism markers tightly linked with the inheritance of cystic fibrosis are deleted on der(7).

Clusters of chromosome 9 aberrations are associated with clinico-pathologic subsets of non-Hodgkin's lymphoma.

In this study we analyzed nonrandom aberrations affecting chromosome 9 in a series of 426 consecutively ascertained, karyotypically abnormal non-Hodgkin's lymphoma (NHL) tumors derived from 407 patients. Cytogenetic abnormalities were correlated with clinical, histologic, and immunologic features. Structural abnormalities of chromosome 9 were identified in 60 specimens derived from 59 patients. The recurring abnormalities among these were associated with 4 clinico-pathologic subsets. The first comprised 7 cases of t(9;14)(p13;q32), 6 of which had small lymphocytic lymphoma, plasmacytoid subtype, and an indolent clinical course. The second group included 12 cases with breaks at 9q11-13 and diffuse lymphomas with a large-cell component and a typical response to combination chemotherapy. The third group was comprised of 7 cases with 9q deletions, with a common deleted region encompassing 9q31-32. These cases were characterized by diffuse B-cell histology, young age, and poor clinical outcome. The fourth subset included 5 intermediate- to high-grade T-cell tumors with breaks at 9q34. This analysis of chromosome 9 aberrations in NHL comprises the first such effort based on a large series of tumors. We identify and report here new clinico-pathologic subsets with shared abnormalities of chromosome 9, which should facilitate new approaches to the analysis of the etiology and clinical behavior of NHL.