Marker chromosomes of the long arm of chromosome 1 in endometrial carcinoma

Cytogenetic studies were performed on endometrial specimens of four patients with hyperplasia, six with adenocarcinoma, and one with a mixed mesodermal tumor. Except for one cell, all 65 cells from the hyperplastic specimens had a normal female karyotype. However, a total of 92 cells from the five adenocarcinoma specimens had chromosome abnormalities, though all 20 cells from a specimen of a well differentiated adenocarcinoma showed a normal karyotype. The chromosome number and morphology of the aneuploid cells had minimal changes. The modal number of chromosomes was pseudodiploid in one case and hyperdiploid in four cases. Three kinds of structural abnormalities involving chromosomes #1 were identified to be of clonal origin: del(1p21) in two cases, tdic(1;16)(p21;q24) in one case, and i(1q) markers in two cases. Because the carcinoma cells had two chromosomes #1 of normal morphology, the presence of the marker chromosome led to partial trisomy or tetrasomy of the long arm of chromosome #1. This involvement may be assumed to represent a karyotypic change characteristic of some adenocarcinomas of the endometrium. Complex karyotypes with many rearranged chromosomes were observed in cells from the mixed mesodermal tumor. The karyotypic differences between endometrial carcinoma and the mixed medodermal tumor suggest that the genesis (and its mechanism) of the former may differ from that of the latter.     

Cytogenetic changes in Wilms' tumors

Cytogenetic analysis of 20 Wilms' tumors using short-term culture techniques were undertaken. Chromosome abnormalities were detected in all tumors. In 19 of 20 cases only minor karyotypic changes were observed within cells with near-diploid chromosome numbers; only one tumor was predominantly hyperdiploid. Rearrangements involving chromosome 1 were the most frequently observed abnormality (in 25%) and often resulted in partial or complete trisomy for the long arm. In 20% of the tumors, abnormalities involving chromosomes 11 and 16 were present. The only other chromosomes frequently involved in structural or numerical changes were #12, and #18. Two discrete tumor foci within the same kidney differed cytogenetically, suggesting an independent origin for each focus. No correlation could be made between specific chromosome abnormalities and tumor stage or histologic subtype. Although constitutional deletion of chromosome region 11p13 has frequently been reported to predispose to Wilms' tumor formation, only two tumors with deletions involving this region were observed. Chromosomes from tumors treated with chemotherapy prior to surgical removal and culture yielded findings similar to those in untreated tumor cells.     

Banded chromosome analysis in patients with treatment-associated acute nonlymphocytic leukemia

We have analyzed G-banded metaphase chromosomes from 20 patients with treatment-associated acute nonlymphocytic leukemia (t-ANLL). Nine patients were previously treated for hematologic malignancies and 11 for solid tumors. The interval from initial therapy to t-ANLL ranged from 35 to 182 mo (median 75.5 mo). Medial age at diagnosis of t-ANLL was 58.5 years. Clonal chromosome abnormalities were found in 19 patients (95%). Loss or partial deletion of the long arm of chromosomes #5 and/or #7 were most common, occurring in nine patients. These abnormalities were associated with hypodiploid complex karyotypes. Other nonrandom abnormalities recurring among karyotypes with abnormalities of chromosome #5 included loss of one #18, partial deletion of the long arm of chromosome #2, ring chromosomes, and a Philadelphia (Ph1) chromosome. We also identified a group of five patients whose only karyotypic abnormality was addition of whole chromosomes. The remaining five patients had other karyotypic abnormalities, the most common of which were structural rearrangements in a pseudodiploid clone. Combined data from our study and the three previously published large series of patients with t-ANLL studied with banding suggest a relationship between karyotype and intensity of prior therapy, with abnormalities of chromosomes #5 and #7 occurring more often in the intensively treated patients.     

Cytogenetic study of ten carcinomas of the bladder: involvement of chromosomes 1 and 11

In direct preparations of ten untreated transitional cell carcinomas of the bladder, chromosomes #1 and #11 were most frequently involved in structural changes (in at least seven tumors each). Three tumors had one or two 11p- chromosomes, and, in other tumors, chromosome #11 had taken part in translocations or isochromosome formation, which, except in one tumor, resulted in a loss of short arm material. Also, there was a tendency for the presence of fewer than expected normal chromosomes #11. Chromosome #1 anomalies are common in most types of tumor; however, chromosome #11 abnormalities, particularly the loss of short arm material, are not common and may thus characterize carcinoma of the bladder, a finding that is of interest in view of the location of an oncogene, c-Ha-ras1, on 11p. Translocations probably involved chromosome #17 in four tumors. Structurally changed chromosomes #3 were seen in four tumors, including one or two 3q- chromosomes in two or possibly three tumors.     

Chromosome analysis of three seminomas

Each of three seminomas revealed chromosome #1 and #12 structural changes in direct preparations and short-term cultures. The #1 changes involved duplication of 1q and loss of 1p; in two, the breakpoint was in the heterochromatic region. The anomaly in #12 was a short arm isochromosome, usually present in duplicate. In one tumor, these were the only structural changes; in the other two, there was also involvement of #7, with extra copies of 7p. In one of these two tumors, a heterochromatic minute was identified after C-banding, and in the other, aside from two different markers containing part of #7, there was a dicentric derived from two chromosomes #15; this tumor proved to be prognostically unfavorable. Three normal chromosomes #1 and XXY sex chromosomes were present in each tumor. Chromosomes #11 and #13 were generally underrepresented, and #12 and #19-22 were over-represented.     

Familial osteosarcoma associated with 13;14 chromosomal rearrangement

Two prepubertal sisters of American Indian origin developed osteosarcoma at 8 and 12 years of age. This familial occurrence, tumor onset prior to puberty, unusual tumor location in one who also had short stature, and ethnic background all suggest an inborn predisposition to bone cancer rather than a chance occurrence. Rearrangements involving chromosomes #13 and #14 were found in both the surviving proband and mother. Comparison of the arm ratio and prometaphase G-banding patterns of the rearranged chromosomes suggests either deletion of band 14q11.2 or pericentric inversion (with breakpoints at 13q12 and 14q11.2) in the proband's rearranged chromosome, but not in her mother's. Her mother, who had no malignancy, had a typical Robertsonian translocation [t(13;14)(p11;q11)]. Three previously reported children with chromosomal abnormalities developed osteosarcoma at unusually young ages, younger even than in reported sibships with osteosarcoma. The most frequently detected cytogenetic abnormalities in sarcoma tumor cells involve chromosomes #13 and #14. In addition, some cases of bilateral retinoblastoma and familial unilateral retinoblastoma, which are known to be at increased risk for osteosarcoma, are associated with tiny deletions on chromosome #13. Thus, there may be a causal relationship between constitutional loss or rearrangement of genetic material at these breakpoints on chromosomes #13 or #14 and development of osteosarcoma in this family that is similar to that seen in patients with small constitutional chromosomal deletions who develop Wilms' tumor and retinoblastoma.     

Break points in chromosome #1 abnormalities of 218 human neoplasms

A survey of 343 break points that lead to chromosome #1 abnormalities in 218 human neoplasms showed that 49.9% were located in or immediately adjacent to the centromeric heterochromatin. Amongst rearrangements with breaks in bands p12–q21 were 27 isochromosomes, 22 translocations of the long arm, and four translocations of the short arm to the heterochromatic regions of other chromosomes, and 35 deletions resulting in chromosomes consisting mainly or solely of one arm. Deletions following breakage at various sites in the short arm of chromosome #1 are frequent in malignancies and are quite often found in cells that are trisomic for the long arm. It is suggested that fragility of chromosomes generated as a result of early events in carcinogenesis may be one source of chromosome rearrangements, including those of chromosome #1, on which selection can operate and give rise to progressively more malignant clones.     

Multiple karyotypic changes in retinoblastoma tumor cells: Presence of normal chromosome No. 13 in most tumors

There are conflicting reports on the frequency in retinoblastoma tumor cells of aberrations involving chromosome No. 13. To quantitate the frequency of various chromosome aberrations, we analyzed the karyotypes from ten retinoblastoma tumors; all tumors contained chromosome abnormalities. Chromosome No. 13 was altered in only two tumors, but the aberrations in these two cases affected different portions of the chromosome. We have concluded that chromosome aberrations affecting chromosome No. 13 are relatively infrequent in retinoblastoma tumors. Chromosome No. 1 was involved in rearrangements in eight tumors; in six tumors the rearrangements lead to trisomy of 1q25-1q32. Seven tumors had aberrations resulting in trisomy of the long arm of chromosome No. 17; the most common aberration was an i(17q) chromosome. Every tumor showed trisomy of the long arm of either chromosome No. 1 or 17. These changes in chromosomes No. 1 and 17 have been observed by others in many different tumors and are not unique to retinoblastoma. In summary, chromosome abnormalities were present in all retinoblastoma tumors studied, but no aberration common to all tumors was found.     

Cytogenetic findings in cell lines derived from four ovarian carcinomas

Six cell lines, established from four primary ovarian carcinomas were examined cytogenetically. The lines varied greatly in their chromosome complement. All cells from the lines were aneuploid, although one cell line contained two populations having a pseudodiploid and a pseudotetraploid modal chromosome number. Every chromosome group was involved with loss and gain of chromosomes, but some individual chromosomes were more prone to aneuploidy than others. Chromosome #6 was the most stable throughout. Structural changes gave rise to many marker chromosomes. Although most markers were random and the majority unidentifiable, some abnormalities of clonal origin were found. Deletions especially of chromosome #1, were the most common change. Further sequential studies may elicit the origin, stability, and timing of the chromosome abnormalities.     

A cytogenetic study of Wilms' tumor

Cytogenetic studies were attempted on a sample of 33 Wilms' tumors using short- and long-term tissue culture techniques; most were studied after 2-13 wk in vitro. Abnormal karyotypes were found in 11 tumors, 10 of which had been treated previously with radiotherapy and/or chemotherapy. Insufficient growth of 17 tumors prevented cytogenetic analysis, and in 5 only normal karyotypes were found. Of the 11 tumors with abnormalities, 9 had modes within the diploid range, 1 was hypertriploid, and 1 showed hypodiploid variation. Except for chromosome #5, all chromosomes were involved in structural and numeric changes. Three tumors showed variation in the short arm of chromosome #11, and abnormalities of chromosomes #1, #3, #7, #9, #10, and #14 occurred in more than one tumor. A predisposition to Wilms' tumor is associated with a constitutional deletion of 11p13. From the present study, it is apparent that a similar cytogenetic change may play a primary role in the development of Wilms' tumor in normal individuals.     

Nonrandom chromosome changes in carcinoma of the cervix uteri. I. Nine near-diploid tumors

Chromosome analysis of G- and C-banded preparations of tumor material, processed by a direct method, from nine primary carcinomas of the cervix with modal chromosome numbers in the range 41–49 showed the nonrandom involvement of certain chromosomes in structural and numerical changes. Besides chromosome No. 1 (six tumors), structural changes involved chromosomes No. 11 (five tumors with variable breakpoints and translocation partners), No. 3 (three tumors) No. 6 (three tumors), and No. 17 (17p+ in two tumors). A small metacentric (present in duplicate in most metaphases of one tumor), which may have been a 5q? (?) (with an interstitial long arm deletion), was seen in five tumors. Additional normal chromosomes included chromosomes No. 1 (one tumor without structural changes in this chromosome showing trisomy 1) and No. 3 (four tumors showing trisomy in the absence of structural changes involving this chromosome). Losses commonly affected the B, D, and G groups, particularly chromosomes No. 13 (three tumors) and No. 21 (six tumors), as well as chromosome No. 18 (four tumors). Two X chromosomes were present in all tumors except the two with the lowest modal numbers, both of which lacked an X chromosome.     

Cytogenetic study in multiple myeloma

Ten patients with multiple myeloma (MM) were studied cytogenetically, using the G-banding technique. It was found that five patients had a normal karyotype, whereas five patients exhibited various chromosomal abnormalities. The presence of marker chromosomes was a consistent finding. Among those, the 14q+ marker chromosome was present in three cases, partial or complete trisomy for 1q was detected in four cases, and chromosome #6 was involved in two cases. In one case the 14q+ marker chromosome was determined to result from a translocation between chromosomes #11 and #14. In one patient with Bence Jones κ multiple myeloma, there was a translocation between chromosomes #2 and #8.     

Cytogenetic studies in twenty human brain tumors: Association of no. 22 chromosome abnormalities with tumors of the brain

The chromosomes were analyzed in cells from twenty cases of primary brain tumors cultured for short periods. There were nine cases with chromosome abnormalities; eight of these showed an abnormality involving a No. 22 chromosome. Three cases each of pituitary adenoma and craniopharyngioma showed no chromosome abnormalities. In five of the seven cases of meningioma studied, hypodiploid clones caused by the loss of 1 to 4 chromosomes were observed. Detailed analysis of the missing chromosomes, revealed the loss of a No. 22 chromosome, an aberration specific for meningioma. Two astrocytomas and a case of oligoden-droblastoma also showed an abnormal No. 22 chromosome. The possible significance of the association of No. 22 chromosome abnormalities with tumors of the brain is discussed in the light of findings, obtained to-date, in the field of tumor cytogenetics.     

Expression of a possible constitutional "hot spot" in sperm chromosomes of a patient treated for Wilms' tumor

Sperm chromosomes were studied in a man who was treated for Wilms' tumor with radiotherapy (RT) and chemotherapy (CT) 18 years ago. Human pronuclear sperm chromosomes were obtained after penetration of zona-free hamster eggs. Eighty-nine sperm chromosome complements were analyzed; 12.4% of them showed structural anomalies. This percentage was statistically different from the one found in our laboratory for controls (p less than 0.05). Five of eleven structurally abnormal metaphases had the same aberration: fission of chromosome #1 with the breakpoint at or near the centromere. Breaks and rearrangements of chromosome #1, often involving the centromere region, are among the most frequent anomalies found in Wilms' tumor cells.     

Cytogenetic studies on acute nonlymphocytic leukemias following polycythemia vera

Chromosome studies were performed on 15 patients suffering from acute nonlymphocytic leukemia (ANLL) and in one patient in a preleukemic state following polycythemia vera (PV). Clonal chromosome abnormalities that were present in all cases were clearly nonrandom and involved chromosomes #1, #5, #7, #8, #9, #11, and #21. A subdivision of ANLL into two categories occurring in the course of PV is proposed from the clinical, hematologic, and cytogenetic data: one resembling de novo ANLL with rapid initial evolution, easy classification into one group of the FAB nomenclature, and simple chromosome abnormalities; the other resembling induced leukemia, often with more progressive initial evolution, difficulty or impossibility of classification into one group of the FAB nomenclature, and complex chromosome abnormalities. The consequences for the commitment level of progenitor cell from which the leukemic clones originate are discussed.     

Cytogenetic studies of esophageal carcinoma cell lines

Although the incidence of cancer of the esophagus is low in the United States, the prognosis of patients with this malignancy is poor, especially when metastases exist. More research concerning the biological characteristics of this tumor is necessary to permit more effective treatment and to determine the etiology. We successfully studied cytogenetically 14 short- and long-term cell lines derived from esophageal carcinoma to determine whether these tumors have nonrandom, unique chromosomal abnormalities. Our results showed that the tumor cells had chromosome numbers clustering around a modal number that varied according to the cell line. The presence in the primary explant of extensive numerical and structural abnormalities involving every chromosome including the sex chromosomes indicate that these abnormalities occur early in the malignant cells. The chromosomes most frequently involved in the structural abnormalities were 1, 9, and 11, each occurring in 13 of the 14 lines, and of three found in 12 of the 14 lines. The major aberrations resulted in deletions of portions of these chromosomes. The most frequent breakpoints for these abnormalities occurred at 3p14, 11q11q12; and 9q11q12 as well as in the centromeric regions of all the acrocentric chromosomes. Another unusual chromosomal marker found in three lines (HCE-1, HCE-3, and HCE-5) was a homogeneously staining region (HSR) that occurred as an extension on 11q12.     

Inherited partial trisomy #15 complicated by neuroblastoma

The proband in this study had multiple congenital malformations and a constitutional 46,XY,-13, + der(13),t(13;15)(q34;q23)mat chromosome complement. A bone marrow aspirate revealed neuroblastoma, and cytogenetic studies on tumor cells revealed, in addition to the partial trisomy #15 and probable partial monosomy #13, hypotetraploidy with a mean chromosome number of 82-84, including 3 or 4 copies of each autosome, 2 X chromosomes, no Y chromosome, and a marker. Translocations involving chromosomes #1, #2, #3, #7, and #14 were present, along with multiple double minutes. The possibility that the inherited partial trisomy #15 (and/or partial chromosome #13 monosomy) predisposed to neuroblastoma and additional chromosome changes in this tumor is discussed.     

Biclonal trisomy 3 in a case of epithelioid cellular lymphogranulomatosis (Lennert's lymphoma)

Biclonal trisomy 3 in a case of epithelioid cellular lymphogranulomatosis (Lennert's lymphoma) was demonstrated by Q-banding polymorphisms of chromosome #3. Seventeen of 19 mitoses with trisomy 3 showed duplication of 1 of the homologous chromosomes and the remaining 2 showed duplication of the other chromosome. It is assumed that both chromosomes #3 independently underwent nondisjunction and that this led to the development of the two abnormal clones. Moreover, there appeared to be a qualitative difference between the two clones, because one of them made up a major proportion and the other a minor proportion of the cells in both of the two samples studied at different times.     

Karyotypic characterization of established cell lines and short-term cultures of human lung cancers

Karyotypic patterns were analyzed from the four major histopathologic groups of human lung cancer: small cell (SCC), squamous cell (SQC), large cell (LCC), and adenocarcinoma (ADC). The studies were performed on banded chromosomes from direct preparations of pleural fluids (one case of SQC and LCC, respectively) and on cell lines. All metaphases were aneuploid and showed highly rearranged chromosomes, with the exception of the direct preparation of the SQC, which was pseudodiploid. The number of marker chromosomes varied-from tumor to tumor. No consistent aberrations could be detected. Special attention was paid to chromosomes 3p-, which was earlier reported to be a characteristic marker chromosome for SCC. We could confirm the presence of that abnormality in two of our six SCC lines. However, we also found a 3p- in a primary SQC culture, in one LCC cell line, and in one ADC cell line. The breakpoint on 3p was not consistent. In some lines, numerical and structural changes of chromosomes #1, #12, #14, and #22 were also noteworthy, although none of these chromosome abnormalities seemed to be correlated to a certain histopathologic group.     

Cytogenetic studies in a canine mammary tumor

In a 9-year-old female dog (Basset Artesian Normand) with a mammary adenocarcinoma, cytogenetic evaluation of tumor cells showed a chromosome number of 76 in most metaphases (95%). The following abnormalities were found: symmetric metacentric chromosomes 1 and 6, centric fusion 3/38, a marker X-chromosome (Xmar) and a biarmed small marker chromosome (mar). In the remaining metaphases (5%) there were additional biarmed marker chromosomes present.