Chromosome abnormalities in malignant histiocytosis

Chromosome and pathologic studies were performed on two patients (a 12-year-old boy and a 62-year-old woman) with malignant histiocytosis (MH). Both patients had chromosome abnormalities in their neoplastic cells: the boy's karyotype was 45,Xp+,-Y,9p+,18q-, and the woman's 48,XX,+16, inv(1),mar(5),6p-,10p+,12q+,i(18q),+i(18q). The boy had typical clinical and pathologic findings of MH, and died without achieving remission by chemotherapy. At the initial stage the woman had the clinical and hematologic findings of MH. Chemotherapy was given, but had no beneficial effects. At the terminal stage the bone marrow (BM) biopsy and aspirate, and the autopsy findings, were consistent with those of non-Hodgkin lymphoma, diffuse large cell type, although some histiocytes or abnormal cells in monocyte-macrophage lineage remained in the BM and the autopsied lymph nodes. This study and a review of data on six other cases have failed to establish any specific chromosome changes in MH.     

Chromosomal abnormalities in T-cell malignant lymphoma

Chromosomal abnormalities of T-cell malignant lymphoma are nonrandom and often complex. Some are common with those of other lymphomas, others are more characteristic for T-cell proliferations. The most frequent chromosomal breakpoints involve chromosomes 6, 1, 2, 9p, 17, and the bands where the TcR genes are localized. The frequent rearrangement of band 14q32 suggests that an oncogene is located within. The main results of molecular studies performed in T-cell malignant lymphomas are summarized.     

Chromosome abnormalities as primary events in human malignant disease: evidence from marker chromosomes

Observations on the chromosomes of cells from 5 human malignant tumors are reported. Each tumor had one or more distinctive marker chromosomes. Marker chromosomes were present in a total of 700 of 711 metaphases from these tumors, which included an early malignant lesion of the cervix showing minimal invasion. Two tumors (a Stage 4 carcinoma of the cervix and a reticulum cell sarcoma, both untreated) yielded preparations of high quality. The 7 best-spread metaphases from the former with the modal number of chromosomes (60) had identical karyotypes, as did 16 from the latter with the modal number of 49. Less extensive data on 13 other tumors, 8 of which had marker chromosomes, are also presented. The data presented here, together with the published data on the chromosomes of cells from human tumors, support the view that human malignant tumors frequently but not invariably arise from a single cell in which chromosome changes have occurred. A carcinoma of the corpus uteri, to which brief reference is made, is a possible exception: Most metaphases had apparently normal karyotypes. The role of chromosome abnormalities (particularly structural changes) in the malignant transformation is discussed. Possible parallels between the chromosome findings in the cells of malignant tumors and those in chronic myeloid leukemia are considered. It is suggested that in tumors there may be both specific changes (perhaps involving chromosomes structurally changed) and coincidental changes. Variation in the coincidental changes might largely account for the wide differences between the karyotypes of different tumors.     

Chromosome 1p abnormalities in B non Hodgkin's lymphoma

Thirteen patients with B-non Hodgkin's lymphoma and abnormalities of the short arm of chromosome 1 were evaluated, to see if this cytogenetic anomaly was associated with a particular subgroup of lymphomas. Large cell lymphoma was found in seven patients (with an immunoblastic component in four cases). Six patients with diffuse small cleaved cell lymphoma of non follicle centre cell origin formed a second group. The chromosome 1 breakpoints in the second group were located between p34 and p36, suggesting that genes located here may be important in the initiation or progression of these lymphomas.     

Chromosome abnormalities in B cell chronic lymphocytic leukemia and their clinical correlations

Cytogenetic analysis was successfully performed on 31 of 40 patients with chronic B cell leukemia. Clonal abnormalities were seen in 16 patients using various culture methods. Fourteen of these had unstimulated cultures established of which 13 had the clonal abnormality. Trisomy 12 was observed in seven patients while a 14q32 translocation was present in four. Race, age, hemoglobin, WBC, percentage of lymphocytes and prolymphocytes in BM and PB, platelets, Smig, lymph node, spleen, liver, pattern of bone marrow infiltration, therapy free interval, and overall survival were all compared. Significant correlations between the presence of clonal abnormalities and prior therapy (p less than 0.005) and an increase in prolymphocytes in bone marrow (p = 0.05) and/or peripheral blood (p = 0.0014) were observed.     

Chromosome abnormalities in tumor cells from patients with sporadic Wilms' tumor

The karyotype of nine of 11 Wilms' tumors was successfully analyzed using chromosome banding techniques. Peripheral lymphocytes had a normal karyotype in all six analyzed cases. Cultured cells from one tumor had a normal karyotype; however, they appeared to be fibroblasts. A chromosome 11 deletion, del(11)(p13p14), similar to that seen in patients with sporadic aniridia, was found as the sole abnormality in cells from one tumor. Abnormalities of chromosome 1 resulting in trisomy for the long arm (q21-q31) were found in five cases. Two of them had a translocation involving 1q and 16q, although the breakpoints in each chromosome appeared to differ in the two cases. Two patients had an isochromosome of the long arm, i(1q), and a fifth case had a duplication of the long arm as a result of karyotypic evolution. Chromosome 16 abnormalities were found in three cases, resulting in the partial monosomy of the long arm, sharing q22 as a common deletion. The same three cases also had trisomy 1q due to an unbalanced translocation of 1q or an i(1q). Trisomy for both chromosomes 9 and 12 were present in three cases. Two patients each had whole or partial trisomy of chromosomes 6, 7, 8, 17, and 18. Our data show that although an 11p deletion can occur as a mutation confined to tumor cells, the most common changes are trisomy for 1q, and less often a deletion of 16q.     

Chromosome abnormalities in patients with hairy cell leukemia

We evaluated chromosomes from 20 patients with hairy cell leukemia (HCL) to ascertain the frequency and type of consistent chromosomal abnormalities. Samples from 17 patients were obtained from peripheral blood cultures grown 24 and 48 hours without phytohemagglutinin, or from bone marrow samples. Two male patients had similar, consistent abnormalities; one patient's karyotype was 46,X,+12; that of the second was 46,X,+C marker. In the latter case, the distal long arm of the C marker most closely resembled chromosome No. 12 from band q14 to q terminal, but the short arm and proximal long arm were of undetermined origin. Both karyotypes lacked the Y chromosome. A third patient had, in one sample, a single abnormal cell with an extra No. 3 and an extra No. 12 (48,XY,+3,+12), and in a later sample, a second cell of poor morphology which also could have been trisomic for no. 12. The two patients with consistent chromosome abnormalities had rapidly progressive disease and a relatively short clinical course from the time of diagnosis (5 and 7 months, respectively). Further data are needed, but the results thus far suggest that patients with consistent chromosome abnormalities could be considered as candidates for aggressive combination chemotherapy.     

Histologic, immunophenotypic and genotypic analyses of bone marrow trephines from patients with non-Hodgkin's lymphoma

Marrow involvement in 20 patients with non-Hodgkin's lymphoma (NHL) were studied by histology, immunophenotypic and genotypic methods. Eighteen of these trephines were histologically involved with recognizable lymphomatous infiltrates and five of these were the primary disease site. In the remaining two cases (with histologically involved lymph nodes) the trephines were uninvolved with tumour. Three B-cell cases expressing surface immunoglobulin (sIg) and/or CD37 and one case not analysed phenotypically showed Ig gene rearrangements. The two remaining cases with B NHL showed no gene rearrangements, however, in one of these the trephine was histologically uninvolved with tumour. Twelve out of 14 T-cell cases were characterized by variable or absent expression of one or more T-cell antigens from the tumour population, one case was negative for all T-cell antigens and the remaining case was not histologically involved with tumour. All three lymphoblastic lymphomas and only 4/11 peripheral T-cell lymphomas (PTCL) cases revealed T-cell receptor (TcR) gene rearrangements. One of the latter cases also exhibited Ig J_H gene rearrangements. This study demonstrates the usefulness of bone marrow trephines (BMT) in histologic, phenotypic and genotypic analyses. However, although genotypic data confirm clonality in B NHL and the lymphoblastic lymphomas there was genotypic heterogeneity within the PTCL group.     

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.     

Chromosome abnormalities in erythroleukemia

Erythroleukemia (EL) is a heterogeneous disease in terms of cell type affected, chromosome abnormalities found in the malignant clone, and clinical course. In this article, cases of erythroid EL from the recent medical literature are reviewed using cytogenetic criteria to distinguish such cases from those of myeloid EL. Although most patients with erythroid EL were elderly men, 20% of the cases occurred in the under-3 age group, where boys and girls were equally affected. Chromosomes 5 and 7 were found to be lost or partially deleted in two thirds of the adult patients only, but not in the pediatric patients; this suggests that EL is associated with cumulative mutagen exposure in adult patients only. It is proposed that cytogenetic criteria may be of use prospectively in distinguishing patients with erythroid EL from those with myeloid EL.     

Chromosome abnormalities in cancer

Karyotypic abnormalities have been described in more than 10,000 human neoplasms analyzed by means of chromosome banding. These aberrations are of three different kinds: primary abnormalities, which are essential in establishing the tumor; secondary abnormalities, which develop only after the neoplasm is established but which nevertheless may be important in tumor progression; and cytogenetic noise, which is the background level of nonconsequential aberrations. These latter changes are, in contrast to the primary and secondary aberrations, randomly distributed throughout the genome. The primary abnormalities, of which more than 100 have been identified, are strictly correlated with particular neoplastic disorders and even with histopathological subgroups within a given tumor type. To these purely cytogenetic data implicating specific genetic changes in carcinogenesis may now be added the growing evidence of molecular specificity emerging from recombinant DNA studies. It appears that both currently known classes of directly cancer-relevant genes, the dominant oncogenes and the recessive anti-oncogenes, are located at precisely those genomic sites that are visibly involved in neoplasia-associated chromosomal rearrangements. The molecular genetic data thus support the cytogenetic conclusion that the distribution of consistently cancer-associated breakpoints reflects the genomic position of genes that, either directly or through the control function they exert, are essential in the proliferation and differentiation of human cells.     

Chromosome aberrations following cytotoxic therapy in patients in complete remission from lymphoma.

The frequency of chromosome aberrations in the peripheral blood of patients successfully treated for Hodgkin's disease (HD) and non-Hodgkin's lymphoma is compared with that seen in age-matched haematologically normal subjects. Findings are considered in relation to risk factors associated with the development of secondary myelodysplastic syndrome (MDS) or acute myeloid leukaemia (AML). Overall aberration frequencies were not significantly increased in patients compared with normal subjects. However, there were differences in aberration type. The frequency of exchanges was significantly higher among patients (P less than 0.01) and the frequency of gaps lower (P less than 0.0005). The mean frequency of exchanges was also greater in patients receiving multiple compared to single courses of therapy (P less than 0.0005) and in patients receiving radiotherapy or combined modality therapy compared to chemotherapy alone (P less than 0.005 and P less than 0.0005). Four patients had aberration frequencies greater than 2 SD above the patient mean. One of these was also found to have a mutation of the ras oncogene. None of the patients has yet developed secondary MDS/AML.