Chromosome abnormalities in peripheral T-cell lymphoma

Data on chromosomal abnormalities in T-cell lymphomas are very rare as compared with those reported in B-cell lymphomas. We performed a cytogenetic study in 71 untreated patients with peripheral T-cell lymphoma, classified according to the criteria of the REAL classification. Fifty-seven patients (80.3%) had abnormal clones, whereas 9 karyotypes (12.7%) showed only normal metaphases; 5 karyotypes (7%) could not be analyzed. Recurrent numerical chromosomal abnormalities comprised +3 (21%), +5 (15.7%), +7 (15.5%), +21 (14%), -13 (14%), +8 (12.2%), +19 (12.2%), -10 (10.5%), and -Y (9% of male patients). Chromosomes involved in structural rearrangements were chromosome 6 (31.5%), mainly due to 6q deletions (19.2%), 1q (22.8%), 7q (22.8%), 9p (19.4%), 9q (19.2%), 4q (19.2%), 3q (19.2%), 2p (17.5%), 1p (17.5%), and 14q (17%). Trisomies 3 and 5 mainly correlated with angioimmunoblastic T-cell lymphoma. Isochromosome 7q, associated with trisomy 8, was present in two cases of hepatosplenic gamma/delta T-cell lymphoma. Rearrangements involving the location of T-cell receptor genes were rarely observed (chromosome band 7q35 was rearranged only in three cases, 14q11 in two cases, and 7p15 in none). No correlation could be found between the cytogenetic findings and histologic subgroup or clinical outcome in these patients. Further studies are needed to understand the significance of these abnormalities in peripheral T-cell lymphoma, and to reach a better evaluation of histologic correlations, as many differences persist between the two major classification systems, KIEL and REAL.     

Chromosome abnormalities in acute lymphoblastic leukemia

Less information is available on the cytogenetic abnormalities in marrow cells of patients with acute lymphoblastic leukemia (ALL) than on abnormalities in acute nonlymphocytic leukemia (ANLL); nonetheless, some patterns of karyotypic change in ALL are evident. Even with banding, about 50% of patients appear to have a normal karyotype. The modal chromosome number tends to be higher in ALL than in ANLL. Every patient with B-cell ALL has had an abnormality of one chromosome No. 14 that involved the translocation of material to the end of the long arm. Among seven reported cases, the translocation was from 8q in three patients and 11q in one. Cells with a haploid or near-haploid (24–35) chromosome number have been reported in five patients with ALL and in four patients in a lymphoid blast crisis of chronic myelogenous leukemia. The karyotype in the four ALL patients whose cells were analyzed with banding was remarkably consistent. All patients had the haploid number, usually with both sex chromosomes, plus an additional No. 10, 18, and 21. Evolution of the karyotype, which occurs in the leukemic cells of about 50% of patients, involves cells of patients who had an initially normal or an initially abnormal karyotype. The evidence regarding a correlation between the presence of an abnormal clone prior to treatment and response to treatment is contradictory at present. Some chromosome abnormalities, such as the presence of a Philadelphia (Ph¹) chromosome, a 14q+ chromosome, or a haploid clone, are associated with a relatively short survival.     

Chromosome abnormalities in 16 Finnish patients with Burkitt's lymphoma or L3 acute lymphocytic leukemia

Eleven patients with Burkitt's lymphoma (BL), i.e., small noncleaved non-Hodgkin's lymphoma, and 5 patients with Burkitt-type acute lymphocytic leukemia (ALL-L3) were selected for chromosome study. Two of the 16 patients had no B-cell markers, but the erythrocyte marker--glycophorin A--was present on the surface of the leukemic blasts. The critical breakpoint at 8q24 was detected in 14 of the 16 patients, whereas this aberration was not detected in any of the 134 patients belonging to other subgroups of non-Hodgkin's lymphoma or ALL that we studied during the same period. In addition to the t(8;14)(q24;q32), the following translocations with the breakpoint at 8q24 were seen: t(2;8)(p11;q24), t(8;11)(q24;q13) in BL, and t(2;8;14)(p11 or p12;q24;q32) in ALL. Additional aberrations seen more than once were trisomy #7 and abnormalities in chromosomes #1, #11, and #13.     

Chromosome abnormalities in patients with chronic myelocytic leukemia

Fifty patients with chronic myelocytic leukemia (CML) grouped into four stages on the basis of clinical and hematological results were analyzed with chromosomal banding techniques. Of the 50 patients, 48 hand the "standard" type of Ph1 translocation, t(9 ; 22) (q34 ; q11) and the remaining 2 had Ph1-negative diploid karyotype. The frequency of numerical chromosomal changes and/or structural chromosomal changes other than the Ph1 translocation varied with the stages; the frequency was 1 of 28 cases (3.6%) for patients in stage I (chronic phase), 5 of 11 (45.5%) in stage II (early stage of blastic phase), 11 of 13 (84.6%) in stage III (blastic phase) and 2 of 7 (28.6%) in stage IV (remission phase). Numerical changes in hyperdiploid leukemic cells correlated well with the appearance of extra #8 and extra Ph1 In 5 cases with hypodiploid leukemic cells, one of the #7 pair was absent in 4 cases and Y in 1 case. As structural changes, partial excess of chromosome 1, isochromosome 17q, isochromosome 1q, tdic (20p+ ; 21q-), del (7) (q11), t(2p+ ; 11p-), #12q+ and Xp+ were observed. Chromosomal analysis alone is not the best marker to diagnose the onset of blastic phase; however, it is a useful parameter when considered in combination with clinical and hematological results.     

Chromosome abnormalities involving heterochromatic regions in monocytic leukemia

We report two cases of monocytic leukemia associated with cytogenetic changes involving the juxtacentromeric heterochromatin of different chromosomes. In a patient with chronic myelomonocytic leukemia (CMMoL) we describe a translocation t(1;9)(q12;q13) in which the duplicated derivative chromosome 9q + showed a huge centromeric C-band, derived by fusion of the heterochromatic regions of chromosomes 1 and 9. The constitutional karyotype showed two heterochromatin polymorphisms, 1qh + and inv(9qh). In the second case, an acute monoblastic leukemia was associated with an abnormally elongated juxtacentromeric heterochromatic region of chromosome 4 that was not constitutionally present.     

Chromosome 21 abnormalities with AML1 amplification in acute lymphoblastic leukemia

Fluorescence in situ hybridization (FISH) studies were performed in three cases of acute lymphoblastic leukemia (ALL) with marker chromosomes to analyze the contribution of chromosome 21 in these markers. FISH with a chromosome 21 painting probe confirmed that chromosome 21 was involved in all three cases. FISH with YAC probes showed that the number of extra copies varied according to their location on chromosome 21. Attention was focused on the AML1 gene, which was present as five copies in most of the cells exhibiting the marker chromosomes. As controls, 11 cases of childhood ALL were studied with PAC probes covering AML1. The results agreed with the banded karyotypes in 10 patients. FISH uncovered a clone with four copies of AML1 which were only observed by FISH analysis of interphase nuclei in one patient. No point mutation was detected in exons 3-5, encoding the runt domain of AML1, in the three cases, suggesting an oncogenic role of wild-type AML1 amplification.     

Chromosome 7 abnormalities in acute megakaryoblastic leukemia associated with Down syndrome

Deletions of the 5′ ABL region adjacent to the t(9;22)(q34;q11) have recently been reported in 8–32.7% of patients with chronic myeloid leukemia (CML). The deletions were visualized with fluorescence in situ hybridization using, in the majority of the cases, the Vysis LSI BCR/ABL ES (extra signal) probe. In our series, 10 of 99 CML patients (10.1%) were characterized by a 5′ ABL deletion. We show that 3′ BCR losses are observed in nearly all the cases with 5′ ABL deletions. Moreover, the different genetic events (Philadelphia chromosome formation; 5′ ABL and 3′ BCR deletions) occur simultaneously in a one-step process without any evidence for genetic instability in the target bone marrow cells.     

Chromosome abnormalities in chronic lymphocytic leukemia revealed by cytochalasin B and Epstein-Barr virus

Peripheral blood lymphocytes from eight patients with chronic lymphocytic leukemia (CLL) were cultured with Epstein Barr virus (EBV) and cytochalasin B. All eight cytochalasin B cultures had analyzable metaphases whereas only six of the EBV cultures were successful. Furthermore, the number of abnormal metaphases and the mitotic indices were greater in the cytochalasin B cultures than in the EBV cultures. Trisomy 12, alone or in combination with other abnormalities, was the most frequent cytogenetic finding. Structural abnormalities of chromosomes #6 and #14 were also found. Cytochalasin B appears to be an effective mitogen for demonstrating abnormal metaphases in patients with CLL.     

Chromosome abnormalities in B-cell prolymphocytic leukemia: A study of nine cases

Chromosome abnormalities were demonstrated in 50–100% of Giemsa-banded metaphases from nine cases of B-cell prolymphocytic leukemia (B-PLL). Mitoses were obtained with pokeweed mitogen following pretreatment of peripheral blood (PB) prolymphocytes with neuraminidase-galactose oxidase. Chromosome 14 was abnormal in eight of the nine cases: a marker 14q+, with breakpoint at band q32 in seven and trisomy 14 in one. In four cases the abnormal No. 14 was one of several primary abnormalities and in four others it was seen in secondary clones. The origin of the translocated material was unknown in three cases, in two it resulted from t(11;14), later becoming t(11;14;21) in one of them, t(1;14) in another, progressing later to t(1;14;17); in yet another patient, the 14q was the result of a complex rearrangement t(6;14;17). Abnormalities of chromosome 6 were seen in six cases; 6q? as the primary abnormality in three; trisomy 6 was part of secondary changes in one case. Structural abnormalities of chromosome 1 were seen in six cases: 1q? in four (in one as the only abnormality), 1q+ in one case, and 1p? in another, both in the main clone. Trisomy 12 was demonstrated in three cases but not as the primary change. Spleen cells in two patients showed a higher frequency of abnormalities than in the PB, supporting the concept of the spleen being the organ primarily involved in B-PLL. Evidence of karyotypic evolution was demonstrated in six patients, in some clearly associated with clinical progression of the disease. The type and frequency of the abnormalities observed in B-PLL resemble those seen in non-Hodgkin's lymphomas and suggest major differences from B-CLL, although a relationship with the latter can not be completely ruled out at present.     

Chromosome abnormalities in chronic lymphocytic leukemia revealed by TPA as a mitogen

Bone marrow and peripheral blood cultures of chronic lymphocytic leukemia patients were mitogenically stimulated with TPA (12-0-tetradecanylphorbol-13-acetate). Clonal cytogenetic abnormalities were detected in frequencies varying from 15% to 100%, in five of the six patients studied. Parallel studies with pokeweek mitogen showed a much lower level of stimulation and only two abnormal clones were detected. The chromosome abnormalities described in this study are similar to those reported in CLL by other authors, particularly with respect to trisomy 12 and deletion 11q. A significant frequency of hypodiploidy and chromosome deletion was also detected in this study, and further studies are underway to determine the significance of these findings.     

Chromosome abnormalities in neuroblastoma

The case is briefly reported of a 7-month-old boy with a disseminated neuroblastoma, whose marrow showed neuroblastoma rosettes and on direct examination on two occasions revealed a high proportion of cells with 48 chromosomes forming an abnormal cell line.     

Chromosome abnormalities in leiomyosarcomas

Short-term cultures from seven soft tissue leiomyosarcomas were investigated cytogenetically. Sufficient mitoses for chromosome analysis were obtained in six cases, four of which had only normal karyotypes. In one tumor, an intramuscular leiomyosarcoma of the lower arm, a variety of nonclonal structural and numerical aberrations were found in two thirds of the metaphases. Another tumor, a subcutaneous leiomyosarcoma of the knee, had clonal abnormalities resulting in the karyotype 46,X,der(X)t(X;4)(:Xq26----cen----Xp22::4q23----4qter) , del(4)(q23)/47,X,der(X)t(X;4),del(4)(q23), + 20. Flow cytofluorometric measurements of the DNA content in the six leiomyosarcomas successfully karyotyped revealed diploid values in five tumors. The leiomyosarcoma displaying numerous nonclonal changes had two cytofluorometric peaks, 1.01 and 1.39, indicating that the metaphases available for cytogenetic study cannot have been fully representative of the tumor stemline.     

Chromosome abnormalities in meningiomas

Cytogenetic analyses of eight meningiomas grown in culture for 1 week are reported. Normal karyotypes were found in three cases and hypodiploidy in the remaining five. In the five hypodiploid meningiomas, one chromosome #22 was missing in four cases, and one case exhibited a 22q- deletion. In four of these five cases, chromosome #14 was either lost or altered. Chromosome #1 was lost or altered in three, and chromosome #6 in two. These findings lend further support for the association of total or partial loss of chromosome #22 in meningiomas and suggest the involvement of other chromosomes in the clonal evolution of these tumors.     

Chromosome abnormalities in pancreatic adenocarcinoma

Adenocarcinoma of the pancreas is the fifth most common cause of cancer deaths in the United States, yet few cytogenetic studies of this tumor have been reported. We analyzed 26 primary tumors to identify which chromosome abnormalities occur most frequently in this neoplasm. One carcinoma was well differentiated and mucin producing, 18 were moderately well differentiated, and seven were poorly differentiated. Only normal karyotypes were obtained from nine carcinomas. The remaining 17 carcinomas frequently had normal metaphase cells in addition to simple to highly complex karyotypes. The modal chromosome number in 20 carcinomas was diploid or near-diploid; four carcinomas had both a major near-diploid and near-triploid or near-tetraploid component, and two were near-tetraploid. Numerical abnormalities included loss of whole copies of chromosomes 6, 17, and 18, and gains of chromosome 20. Structural abnormalities were frequent, with 1p, 2p, 3p, 4q, 6q, 7q, 1 1q, and 17p recurrently involved. Results of this study were combined with karyotypes of 19 other primary adenocarcinomas of the pancreas reported in the literature. The combined data involving 1 17 breakpoints suggest that careful analysis of chromosome 20, proximal 1 q. 6q, proximal 8p. and proximal 17p could be productive in defining genes involved in adenocarcinoma of the pancreas. Genes Chrom Cancer 9:93-100 (1994).© 1994 Wiley-Liss, Inc.