Abnormalities of chromosome No. 1: Two cases with lymphocytic lymphomas

Two cases of lymphocytic lymphoma with a duplication of part of the long arm of chromosome #1, between bands 1q25 and 1q32, are presented. The coincidence between this finding with others in the literature supports the concept that this specific chromosome segment is related to the proliferative advantage of malignant cells in neoplasia.     

Two 14q+ chromosomes in malignant lymphoma: crucial cytogenetic changes on 14q

We encountered a 36-year-old white male patient with poorly differentiated lymphocytic lymphoma, whose lymph node cells showed a clonal cytogenetic change involving chromosome #14, i.e., 47,XY, + 2,der(14),t(14;14)(14pter----14q32;14q24----14q32++ +). In addition to this change, cells with a translocation between chromosomes #2 and another #14 [t(2;14)(q21;q24)], as well as a missing chromosome #8 were found. We have reviewed the literature dealing with two or more changes affecting chromosome #14 and discussed the importance of the cytogenetic change at band 14q32 in malignant lymphoma.     

Marker chromosome 1q+ in acute lymphocytic leukemia

This paper presents the results of a cytogenetic analysis on a patient with acute lymphocytic leukemia (ALL) type L2 according to the FAB classification. Of the metaphases examined, 69.3% belong to the aberrant clone of pseudodiploid karyotype. Marker chromosome 14q+ has been identified in all the cells of the clone. Duplication was found in 30% of the metaphases, and in 15% triplication of the proximal segment of the long arm of chromosome #1 (q11-q21). In one metaphase the long arm of chromosome #1 is made up of segment q11-q21 four times repeated. Aberrations of chromosome #1 support the idea that heterochromatic region may be related to the higher degree of the cell malignity.     

Unusual translocation and chronic myelocytic leukemia: “masked” Philadelphia chromosome (Ph1)

An unusual Ph¹ translocation in a woman, 65 years old, with chronic myelocytic leukemia is reported. Cytogenetic analysis performed on 150 mitoses examined with Q?, R?, and C-banding revealed evidence for an unusual translocation involving the insertion of a segment of chromosome #9 into chromosome #22, thus masking the presence of a Ph¹. The anomaly can best be described as 46, XX, ins(22;9) (q11;q22→34).     

Novel tandem triplication of 1q in a patient with a myelodysplastic syndrome

This is a report of a patient with a myelodysplastic syndrome characterized by symptomatic neutropenia whose bone marrow aspirates have consistently demonstrated an unusual cytogenetic anomaly. The abnormality present in all metaphases consisted of a tandem triplication of a portion of the long arm of chromosome #1, resulting in tetrasomy of a section of this chromosome (1q21–32). Duplications of this portion of chromosome #1 were observed as a nonrandom event in various malignant states. In addition, these precise breakpoints can be increasingly correlated with tandem duplications.     

Jumping translocation of chromosome 14 in a skin squamous cell carcinoma from a xeroderma pigmentosum patient

The cytogenetic study of a case of cutaneous squamous cell carcinoma developed in a child affected by xeroderma pigmentosum is described. In this paratetraploid tumor, virtually all mitoses had the following rearrangements: i(1q), i(1p), t(3q14q), del(9p), and der(19)t(8;19). In addition, there were several deletions of 1p and 1q. The del(9p) likely occurred as the first rearrangement. The distal segment of the short arm of chromosome #9 and the long arm of #19 and #22 were the most underrepresented and chromosome #6 the most overrepresented chromosome or chromosome segment. The most striking anomaly detected was a jumping translocation of chromosome #14, involved with chromosomes #1, #3, #5, #7, #9, #14, and #22. The breakage of chromosome #14 always occurred on the short arm.     

Chromosomal composition of four permanent cultured cell lines derived from human gliomas

Four permanent cell lines derived from malignant human gliomas were karyotyped using Giemsa-trypsin banding. D-65 MG had a stemline with 44 chromosomes, including 11 markers: 1p+, 2q-, 3p-, 3q+, 4p-, 9q-, 11q+, 15q-, 17p+, 21p+, 22q-. The net effect after accounting for fragments in markers was: +8, -10, -16 -X. D-32 MG had chromosome counts 90-91 without a distinct stem karyotype. Modal cells contained from 3 to 5 copies of the normal autosomes and 5 markers: 1q-, 3q-, 7q-, 13q-, 18q-. D-32 MGCl2 had a complex karyotype containing 78-82 chromosomes. There was no stemline, and modal cells varied from one another primarily in their set of marker chromosomes. A total of 23 markers were seen in this line, 17 of which were present in most modal cells. They were partially characterized as: 1q+, 1q+, 2q-, 5q+, 7p-, 7q-, 8p+, 8p+, 9p+, 12p+, 14q-, 16q+, 19q+, 19q+, a small submetacentric chromosome of undetermined origin and two small isochromosomes, i(Dp or Gp) and i(17p or 18p). A-172 MG had a modal peak of 77 chromosomes within which no two cells were exactly alike. Ten markers seen in modal cells were: 1p-, 4p+, 6p+, 6p+, 6q-, 7p-, 9p-q+, 13q+ 14p+, 22q+. There were no normal copies of chromosomes #1, #6, #9, #14. These four glioma-derived cell lines possess unique karyotypes, but each displays some combination of the numerical and structural deviations generally associated with established glioma lines.     

Cytogenetics of human malignant melanoma and premalignant lesions

Chromosome studies were done on direct preparations, early passage cultures, and/or cell lines derived from melanocytic lesions of 17 patients. There were 5 nevi (3 dysplastic); 1 early primary melanoma (radial growth phase); 1 advanced primary melanoma (vertical growth phase) with multiple metastases; and 10 metastatic lesions. The 5 nevi had normal karyotypes, while each of the tumors had a predominantly abnormal karyotype. The early melanoma was pseudodiploid, including a 6p;22 translocation. Ten of the 11 advanced melanomas had one or more aberrations involving chromosome #1, with 9 having deletions or translocations of Ip that involved the proximal segment 1p12→1p22 9 times in 8 lesions. Six advanced tumors had additional material involving 7q, including extra #7s (4 cases) and 7q (2 cases). Nine melanomas, including the early tumor, had alterations in chromosome #6. Three had additional copies of 6p (as iso6p or t6p); the others showed no consistent pattern. In one advanced tumor, the primary lesion and 5 metastases (removed seriatim over an 18-month period) had nearly identical karyotypes, indicating the clonal nature of the neoplasm. The nonrandom cytogenetic changes suggest that genes important in melanoma carcinogenesis are located on the proximal portion of 1p, on 7q, and on chromosome #6. More data on early lesions are needed to identify the relation of these various cytogenetic changes to the different stages of malignant melanoma development.     

Cytogenetic findings in congenital leukemia: case report and review of the literature

The cytogenetic findings in a five-week-old female infant with acute lymphoblastic leukemia (ALL) are reported. Markers 11q - and 19 + were observed and considered to be due to an interstitial deletion of segment 11q13 to 11q23 of chromosome #11 and an insertion of this segment into the terminal region of the short arm of #19. Previously published banded cases of leukemic infants under one year of age have been summarized. A review of the data in these 29 cases suggests that the appearance of a normal karyotype in acute leukemia of infants (less than or equal to 1 year old) is much less common than in other categories of acute leukemia. Fourteen out of 29 cases (48%) had chromosomal abnormalities involving 11q. Seven of eight ALL cases had aberrations with a breakpoint at 11q22-23; six cases had t(4;11), one case had a del(11q) and ins(19p), and another had a t(1;22;4). All of three AMMoL cases had translocations involving the long arm of #11. The percentage of patients with t(4;11) and certain translocations involving 11q in infants with ALL or AMMoL, respectively, is higher than that seen in ALL and AMMoL in general. Eleven out of 12 cases (92%) of infant acute leukemias with chromosomal abnormalities involving 11q22-23 were five months old or less.     

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.     

Genomic instability in multiple myeloma: evidence for jumping segmental duplications of chromosome arm 1q

Multiple myeloma (MM) is a malignant plasma cell disorder characterized by complex karyotypes and chromosome 1 instability at the cytogenetic level. Chromosome 1 instability generally involves partial duplications, whole-arm translocations, or jumping translocations of 1q, identified by G-banding. To characterize this instability further, we performed spectral karyotyping and fluorescence in situ hybridization with probes for satII/III (1q12), BCL9 (1q21), and IL6R (1q21) on the karyotypes of 44 patients with known 1q aberrations. In eight patients, segmental duplication of 1q12-21 and adjacent bands occurred on nonhomologous chromosomes. In five cases, the 1q first jumped to a nonhomologous chromosome, after which the 1q12-21 segment again duplicated itself 1-3 times. In three other cases, segmental duplications occurred after the 1q first jumped to a nonhomologous chromosome, where the proximal adjacent nonhomologous chromosome segment was duplicated prior to the 1q jumping or inserting itself into a new location. These cases demonstrate that satII/III DNA sequences are not only associated not only with the duplication of adjacent distal chromosome segments after translocation, but are also associated with the duplication and jumping/insertion of proximal nonhomologous chromosome segments. We have designated this type of instability as a jumping segmental duplication.     

Chromosome changes in metastatic human melanoma

Cytogenetic studies were performed on human malignant melanoma cells from eight metastatic lesions. Five tumors displayed near-triploid and three near-diploid chromosome numbers. Chromosomes #1,#6,#7, followed by #2 and #9, were found to be most frequently involved in structural aberrations. Aberrations involving chromosome #1, with deletions or translocations of 1p, involving region 1p12-1p22 in seven of eight breakpoints of the p arm were observed. Seven of nine breakpoints of 6q were located at region 6q15-6q21. Most of the breakpoints on chromosome #7 occurred near the centromeric region. All tumors had additional chromosome material involving 1q, chromosome #7 (7q in two tumors), and in five tumors an increased dose of chromosome #6 (6p in one tumor). The nonrandom breakpoints of these and other chromosomes involved diverse bands, including loci of oncogenes and fragile sites. The observation of nonrandom chromosomal changes in advanced malignant melanoma suggests that genes important in the progression of melanoma are located on chromosomes #1,#6, and #7.     

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.     

Abnormalities of chromosome #13 in retinoblastomas from individuals with normal constitutional karyotypes

Constitutional chromsome abnormalities have been associated with retinoblastoma, Wilms' tumor, and a familial form of renal cell carcinoma. For each tumor type, the particular chromosome segment involved in the observed rearrangements is different: in retinoblastoma, that segment is band q14 on chromosome #13. We now present evidence that in retinoblastoma, structural abnormalities involving the particular chromosome segment identified in the constitutional cases can also occur in the tumors of individuals with normal constitutional karyotypes. Six cases with retinoblastomas in one or both eyes were analyzed; deletions/rearrangements involving 13q14 were found in the tumor cell karyotypes of five of the six. These observations suggest that changes in a gene or genes at a common site (13q14) play a role in tumorigenesis in all forms of retinoblastoma, sporadic as well as heritable.     

Chromosome #14 markers in two Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines of normal origin differ from the Burkitt lymphoma (BL)-associated 14q+ marker

Two among ten Epstein-Barr Virus (EBV)-transformed lymphoblastoid cell lines contained a 14q+ marker in a low frequency of the cells (2 and 9%). By means of "mesome-prosome" analysis of the G-band patterns of these markers; it was established that the additional chromosome segments of these two 14q+ markers came from chromosomes #3 and #5, respectively, and not from chromosome #8 as in the 14q+ marker of Burkitt lymphoma. Chromosome #8 was not involved at all in any changes in the ten lymphoblastoid cell lines studied.     

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.     

Cytogenetic analysis in human breast carcinoma. I. Nine cases in the diploid range investigated using direct preparations

Cells in mitosis were found in 51 of 110 (47%) breast tumor samples; karyotypes of nine tumors in the diploid range are presented. The simplest stemline karyotype found was 46,XX,?16,+del(1)(qter→p21). The chromosome homologues most frequently lost were #8, #13, and #16. Monosomy or partial monosomy for chromosome #16 was seen in six cases, including the two simplest and chromosome #16 might be of relevance for initiation of malignant transformation in breast carcinoma.The only chromosome feature common to all nine breast carcinomas was the presence of a marker involving the long arm of chromosome #1, the region shared by all being 1qter→1q21.     

A 14q+ chromosome in adult T-cell leukemia

Chromosome studies were conducted on two patients with adult T-cell leukemia. In both patients, a marker chromosome 14q+ and a structural change involving chromosome 1 with trisomy of the q arm were found in peripheral blood leukocytes. The 14q+ marker chromosome had resulted from translocation from #5p in one patient and #5q in the other patient. The present and previous studies suggest that the donor chromosomes involved in the 14q+ translocation are variable. This indicates that the 14q+ marker chromosome rather than the donor chromosome is intimately related with adult T-cell leukemia.     

Noninvolvement of chromosome 16 in karyotype evolution of acute myeloid leukemia in a patient with a heritable fragile site on 16q22

A fragile site on the long arm of chromosome #16 (q22) was detected in a 24-year-old man with pancytopenia. During the course of the disease he developed an inverted duplication of region q11-12 of chromosome #1 and a translocation between chromosomes #9 and #13: t(9;13)(p22;q32). These abnormalities, as well as an additional iso-like marker chromosome that consisted of one normal 9p and the abnormal 9p arm, were detected in Epstein-Barr nuclear antigen-positive B-cell cultures. Two years later, evolution of the abnormal clone with loss of chromosome #7 and, subsequently, chromosome #22 occurred in connection with development of acute myeloid leukemia. Although the heritable fragile site on chromosome #16 was present in all cell populations investigated, it was not involved in the evolution of the abnormal karyotype. This fragile chromosome #16 also was found in 4 of 11 family members in whom chromosome analysis was performed, thus suggesting this aberration was inherited in a dominant autosomal pattern. The incidence of the heritable fragile site in normal and leukemic cells of the patient, as well as stimulated blood cultures of his relatives, are reported. In addition, the possible relationship between this constitutional chromosome breakage syndrome and the occurrence of leukemia is analyzed.     

Homozygosity for 8pter----q22 in acute myeloblastic leukemia with t(8;21)(q22;q22)

A case of acute nonlymphocytic leukemia with homozygosity for the chromosome segment 8pter----8q22 is reported. A t(8;21)(q22;q22) translocation was associated with duplication of the derivative chromosome 8q- and absence of the normal chromosome 8. These rearrangements also yielded hemizygosity for 8q22----qter. This case shows that acquired hemizygosity and homozygosity do exist in leukemia as in solid malignant tumors.