Cytogenetic characterization of tumors of the vulva and vagina

Neoplasms of the vulva and vagina account for less than 5% of all female genital tract cancers. Squamous cell carcinoma (SCC) represents more than 70% of the cases in both locales, followed by melanoma, basal cell carcinoma, Paget's disease, and other carcinoma subtypes. Until recently, only few cases had been analyzed by chromosome banding techniques and karyotyped, and also the number subjected to molecular cytogenetic analysis remains low. To understand better the genetic changes harbored by the neoplastic cells in cancer of the vulva and vagina, we analyzed cytogenetically 51 such tumors, finding karyotypic abnormalities in 37. All tumors were analyzed by G-banding, sometimes supplemented by multicolor fluorescence in situ hybridization, and a subset of tumors was also analyzed by comparative genomic hybridization. The two cytogenetically abnormal cases of Paget's disease both had two clones, one with gain of chromosome 7 as the sole change, the other with loss of the X chromosome among, in one case, other aberrations. The four cytogenetically abnormal malignant melanomas (three of the vulva, one of the vagina) presented complex karyotypes with aberrations involving different chromosomes but most often chromosome 1, specifically 1p12-q41. In the 31 cytogenetically abnormal SCCs, different clonal karyotypic abnormalities were seen. Intratumor heterogeneity with multiple clones was observed in 11 cases. The clones were cytogenetically unrelated in eight tumors but related in three, indicating that in the latter clonal evolution had taken place from a single malignantly transformed cell. The main chromosomal imbalances were gains of, or from, chromosome arms 3q, 5p, 8q, 9q, and 19q, and loss from 11q. Breakpoint clusters were seen in 11q13-23, 2q22-35, and 19q13, as well as in the centromeres and pericentromeric bands of chromosomes 3, 8, 9, 13, 14, and 22.     

Karyotypic characterization of urinary bladder transitional cell carcinomas

Samples from 34 primary transitional cell carcinomas (TCCs) of the bladder were short-term-cultured and processed for cytogenetic analysis after G-banding of the chromosomes. Clonal chromosome abnormalities were detected in 27 tumors and normal karyotypes in 3, and the cultures from 4 tumors failed to grow. Losses of genetic material were more common than gains, indicating that loss of tumor suppressor genes may be of major importance in TCC pathogenesis. There was no clonal heterogeneity within individual tumors, consonant with the view that TCCs are monoclonal in origin. The most striking finding was the involvement of chromosome 9 in 92% of the informative cases, as numerical loss of one chromosome copy in 15 cases, but as structural rearrangement in 8. The changes in chromosome 9 always led to loss of material; from 9p, from 9q, or of the entire chromosome. A total of 16 recurrent, unbalanced structural rearrangements were seen, of which del(1)(p11), add(3)(q21), add(5)(q11), del(6)(q13), add(7)(q11), add(11)(p11), i(13)(q10), del(14)(q24), and i(17)(q10) are described here for the first time. The karyotypic imbalances were dominated by losses of the entire or parts of chromosome arms 1p, 9p, 9q, 11p, 13p, and 17p, loss of an entire copy of chromosomes 9, 14, 16, 18, and the Y chromosome, and gains of chromosome arms 1q and 13q and of chromosomes 7 and 20. The chromosome bands and centomeric breakpoints preferentially involved in structural rearrangements were 1q12, 2q11, 5q11, 8q24, 9p13, 9q13, 9q22, 11p11, and 13p10. Rearrangements of 17p and the formation of an i(5)(p10) were associated with more aggressive tumor phenotypes. There was also a general correlation between the tumors' grade/stage and karyotypic complexity, indicating that progressive accumulation of acquired genetic alterations is the driving force behind multistep bladder TCC carcinogenesis.     

A malignant triton tumor with an unbalanced translocation (1;13)(q10;q10) and an isochromosome (8)(q10) as the sole karyotypic abnormalities

The karyotype of a malignant nerve sheath tumor with rhabdomyosarcomatous differentiation (malignant triton tumor) of a 58-year-old woman is reported. The tumor revealed an isochromosome for the long arm of chromosome 8 and an unbalanced translocation (1;13)(q10;q10) leading to a gain of the long arm of chromosome 1 as the sole karyotypic abnormalities.     

Nonrandom pattern of cytogenetic abnormalities in squamous cell carcinoma of the larynx

Cytogenetic analysis of short-term cultures from 105 squamous cell carcinomas of the larynx (LSCC) revealed clonal chromosome aberrations in 56 tumors. Simple karyotypic changes (less than four aberrations per clone) were found in 24 cases, and the remaining 32 tumors had complex karyotypes with multiple numerical as well as unbalanced structural rearrangements. Extensive intratumor heterogeneity, in the form of multiple related subclones or unrelated clones, was observed in a large fraction of the tumors. The structural changes most often affected chromosomes 3, 1, 11, 7, 2, 15, 5, 4, 8, and 12, with rearrangements in the centromeric regions, i.e., the centromeric bands p10 and q10 and the juxtacentromeric bands p11 and q11, accounting for 43% of the total breakpoints. The most common imbalances brought about by numerical and unbalanced structural rearrangements were loss of chromosomal region 3p21-pter, chromosome arms 4p, 6q, 8p, 10p, 13p, 14p, 15p, and 17p, and gain of chromosomal regions 3q21-qter, 7q31-pter, and 8q. Among 17 recurrent aberrations identified, the most common were i(8q), hsr(11)(q13), i(3q), i(5p), and del(3)(p11). No statistically significant association was found between major karyotypic features and histological differentiation or TNM stage. The karyotypic features of the LSCC were also compared with previously published oral SCC, a subgroup of SCC that has been more extensively characterized cytogenetically. No clear-cut karyotypic differences were found between LSCC and oral SCC, with the exception that i(8q) was significantly more frequent among the latter.     

Cytogenetic analysis of pancreatic carcinomas: Intratumor heterogeneity and nonrandom pattern of chromosome aberrations

Twenty-nine nonendocrine pancreatic carcinomas (20 primary tumors and nine metastases) were studied by chromosome banding after short-term culture. Acquired clonal aberrations were found in 25 tumors and a detailed analysis of these revealed extensive cytogenetic intratumor heterogeneity. Apart from six carcinomas with one clone only, 19 tumors displayed from two to 58 clones, bringing the total number of clones to 230. Karyotypically related clones, signifying evolutionary variation, were found in 16 tumors, whereas unrelated clones were present in nine, the latter finding probably reflecting a distinct pathogenetic mechanism. The cytogenetic profile of pancreatic carcinoma was characterized by multiple numerical and structural changes. In total, more than 500 abnormal chromosomes, including rings, markers, homogeneously stained regions, and double minutes, altogether displaying 608 breakpoints, were detected. This complexity and heterogeneity notwithstanding, a nonrandom karyotypic pattern can be discerned in pancreatic cancer. Chromosomes 1, 3, 6, 7, 8, 11, 12, 17, and 19 and bands 1q12, 1q21, 3q11, 6p21, 6q21, 7q11, 7q22, 7q32, 11q13, 13cen, 14cen, 17q11, 17q21, and 19q13 were most frequently involved in structural rearrangements. A total of 19 recurrent unbalanced structural changes were identified, 11 of which were not reported previously: del(1)(q11), del(3)(p11), i(3)(q10), del(4)(q25), del(11)(p13), dup(11)(q13q23), i(12)(p10), der(13;15)(q10;q10), del(18)(q12), del(18)(q21), and i(19)(q10). The main karyotypic imbalances were entire-copy losses of chromosomes 18, Y, and 21, gains of chromosomes 7, 2, and 20, partial or whole-arm losses of 1p, 3p, 6q, 8p, 9p, 15q, 17p, 18q, 19p, and 20p, and partial or whole-arm gains of 1q, 3q, 5p, 6p, 7q, 8q, 11q, 12p, 17q, 19q, and 20q. In general, the karyotypic pattern of pancreatic carcinoma fits the multistep carcinogenesis concept. The observed cytogenetic heterogeneity appears to reflect a multitude of interchangeable but oncogenetically equivalent events, and the nonrandomness of the chromosomal alterations underscores the preferential pathways involved in tumor initiation and progression. Genes Chromosomes Cancer 23:81–99, 1998. © 1998 Wiley-Liss, Inc.     

Karyotypic characterization of colorectal adenocarcinomas

Cytogenetic analysis of short-term cultures from 52 primary colorectal adenocarcinomas revealed clonal chromosome aberrations in 45 tumors, whereas the remaining 7 had a normal karyotype. More than 1 abnormal clone was detected in 26 tumors; in 18 of them, the clones were cytogenetically unrelated. The modal chromosome number was near-diploid in 32 tumors and near-triploid to near-tetraploid in 13. Only numerical aberrations were identified in 13 carcinomas, only structural aberrations in 3, and 29 had both numerical and structural changes. The most common numerical abnormalities were, in order of decreasing frequency, gains of chromosomes 7, 13, 20, and Y and losses of chromosomes 18, Y, 14, and 15. The structural changes most often affected chromosomes 1, 17, 8, 7, and 13. The most frequently rearranged chromosome bands were, in order of decreasing frequency, 13q10, 17p10, 1p22, 8q10, 17p11, 7q11, 1p33, 7p22, 7q32, 12q24, 16p13, and 19p13. Frequently recurring aberrations affecting these bands were del(1)(p22), i(8)(q10), i(13)(q10), and add(17)(p11–13). The most common partial gains were from chromosome arms 8q, 13q, and 17q and the most common partial losses from chromosome arms 1p, 8p, 13p, and 17p. A correlation analysis between the karyotype and the clinicopathologic features in our total material, which consists of altogether 153 colorectal carcinomas, including 116 with an abnormal karyotype, showed a statistically significant association (P < 0.05) between the karyotype and tumor grade and site. Carcinomas with structural chromosome rearrangements were often poorly differentiated; well and moderately differentiated tumors often had only numerical aberrations or normal karyotypes. Abnormal karyotypes were more common in rectal carcinomas than in carcinomas situated higher up. Near-triploid to near-tetraploid karyotypes were more than twice as frequent in tumors of the distal colon as in those of the proximal colon and rectum. The cytogenetic data indicate that carcinomas located in the proximal colon and rectum, which often are near-diploid with simple numerical changes and cytogenetically unrelated clones, probably arise through different mechanisms than do tumors located in the distal colon, which more often have complex near-triploid to near-tetraploid karyotypes.     

Two apparent Philadelphia chromosomes arising from translocations with different chromosomes in a patient with CML: 46,XY,t(7;22)(p22;q11),t(9;22)(q34;q11)

Chromosome studies on bone marrow cells and unstimulated peripheral lymphocytes from a patient with chronic myelogenous leukemia revealed the presence in all cells of two apparent Philadelphia chromosomes: one resulting from the classical translocation with a chromosome #9, and the other arising from a translocation between chromosomes #22 and #7. There was no normal chromosome #22. Some of the cells also had an i(17q), indicative of blast crisis. Repeated chromosome studies at different times during the course of the disease revealed the evolution of additional karyotypic changes. All cells from later samples had an extra #8; some of these cells had a third Philadelphia chromosome, whereas, others had a second Y chromosome. Although a few normal cells were seen in PHA-stimulated lymphocyte cultures, indicating that the patient has a normal constitutional karyotype, most of the cells had a karyotype identical to that found in unstimulated cultures. This unusual karyotype, 46,XY,t(7;22)(p22;q11),t(9;22)(q34;q11), represents the first case in which two apparent Philadelphia chromosomes are present in the leukemic cells from a patient in the absence of a normal #22 chromosome.     

Cytogenetic changes at 11q11, 11q23, and 17q11 in myelodysplastic syndrome

Cytogenetic studies were performed on two patients with myelodysplastic syndromes. One patient was a 68 year old Japanese male in whose bone marrow cells two translocations were established, i.e., t(4;11)(q13;q23) and t(11;17)(q11?;q11), as well as other karyotypic changes (-6,-18,15p+). The other patient was a 74 year old white male whose bone marrow cells showed six marker chromosomes, i.e., der(5),t(5;17)(q12;q11), der(6),t(6;5)(q27;q22), der(8),t(8;11;?)(q11;q11----q23;?), der(11),t(11;?)(q11;?), an isochromosome of the long arm of chromosome #8, and a small G-group sized marker chromosome of unknown origin. Though the translocation patterns in the abnormal cells in these two cases were different, the breakpoints of the marker chromosomes were almost the same, i.e., 11q11, 11q23, and 17q11. Also, changes of chromosome #6 were observed; the first case showed monosomy 6 and the second a 6q+ marker chromosome. In these two cases of myelodysplastic syndromes, common sites of chromosome breakage and reunion of 11q23 and 17q11 were close to recently established sites of human cellular oncogene homologs, c-ets (11q23) and c-erbA (17q21----24). These associations draw attention to a possible relationship between chromosome changes in myelodysplastic syndromes and oncogene (or other gene) activation and/or dysfunction.     

Cytogenetic abnormalities in 106 oral squamous cell carcinomas

We report karyotypic features of 106 short-term cultured oral squamous cell carcinomas (SCC), 51 new and 55 previously reported cases, with clonal chromosome aberrations. The major cytogenetic findings were as follows: simple karyotypic changes were present in 38 cases (36%) and 68 tumors (64%) displayed complex karyotypes. The most common numerical changes were +7, +8, +9, +16, +18, +20, and -4, -10, -13, -14, -18, -19, -21, -22, and -Y. Structural rearrangements frequently (43% of the breaks) affected the centromeric regions, resulting in the formation of isochromosomes and whole-arm translocations. Among the recurrent structural aberrations identified, the most common were i(1q), i(3q), i(5p), i(8q), del(16)(q22), and hsr. With the exception of chromosomal band 11q13, which was involved in 25 tumors, only centromeric or near-centromeric bands were commonly involved: 3p11 approximately q11 (59 cases), 8p11 approximately q11 (57), 1p11 approximately q11 (48), 13p11 approximately q11 (46), 5p11 approximately q11 (41), 14p11 approximately q11 (41), and 15p11 approximately q11 (37). Losses of genetic material dominated over gains. The most frequent imbalances included loss of 2q33 approximately qter, 3p, 4p, 6q, 8p, 10p, 11q, 13p, 14p, and 15p, and chromosomes 18, 21, 22, and Y, and gain of chromosomes 7 and 20, 8q, and 11q13. No major karyotypic differences could be discerned between the present series of oral SCC and a previously reported series of laryngeal SCC, indicating that common genetic pathways are involved in the initiation and progression of SCC irrespective of site of origin.     

Chromosome abnormalities in non-small cell lung cancer pleural effusions: Cytogenetic indicators of disease subgroups

A cytogenetic study of pleural effusions (PE) containing metastatic or invasive tumor cells from 11 patients with non-small cell lung cancer (NSCLC) (3 squamous cell carcinomas [SQC] and 8 adenocarcinomas [ADC] including 1 giant cell variant) was performed to identify non-random chromosome abnormalities. Numerical abnormalities seen in ≥ 30% of cases included gain of chromosomes 7 and 20, and loss of chromosomes 4, 9, 10, 13, 15, 16, 18, 19, 21, and 22. The most frequent structural abnormality involved rearrangement in 1p with breakpoints clustering at 1p10-p13. Other recurrent breakpoint regions, seen in ≥ 30% of cases, occurred in chromosome regions 3p10-p21, 3q11-q25, 6p11-p25, 6q13-q23, 7q11-q36, 9q32-q34, 11p11-p13, 11q13-q24, 13p/14p and/or 15p, 17p and 19p, with, in particular, apparent loss of 6q21-q27, 3p21-p26, 7q21-q22, 9p22-p24 (shortest regions of common overlap) and 17p. There was also recurrent gain of 1q23-q44, 8q13-q24, and 11q13-q23. These abnormalities were not restricted to a particular histological subtype, with the exception of + 8 and a breakpoint in 9q32-q34, which were seen only in ADC. The 9q32-q34 breakpoint observed in 4 ADC PE (including 1 giant cell variant) represents a new observation in NSCLC. These findings, when compared to those reported for primary NSCLC indicate cytogenetic differences between the two which may be associated with pleural invasion of NSCLC. © 1993 Wiley-Liss, Inc.     

Consistent chromosomal losses in head and neck squamous cell carcinoma cell lines

Clonal chromosomal abnormalities were characterized in nine cell lines established from squamous cell carcinomas of the head and neck. Aneuploidy was a common feature; one cell line was near-diploid, three were near-triploid, four were near-tetraploid, and one cell line showed extensive variation in chromosome numbers. Consistent numerical abnormalities included loss of the sex chromosomes in six cell lines, losses of chromosomes 2 and 21 in six and five cell lines, respectively, and gain of chromosome 20 in five cell lines. Recurrent structural rearrangements included del(10)(q22-q26) (seven cell lines), i(5)(p10) (six cell lines), i(8)(q10) (six cell lines), add(19)(q13) (six cell lines), del(4)(q21-q31.3) (five cell lines), i(3)(q10) (four cell lines), del(12)(p11.1-p12) (four cell lines), and add (18)(q21-q23) (four cell lines). Other changes were noted in lower frequencies. Loss of specific regions on chromosomes 2, 3p, 4q, 5q, 8p, 10q, 12p, 18q, 19q, and 21 suggests that they may represent sites of putative tumor suppressor genes, loss of which may play a role in the pathogenesis of squamous cell carcinomas of the head and neck. Alternatively, gain of chromosomal region 3q, 5p, and 8q due to isochromosome formation suggests that more than one mechanism is involved in malignant transformation. Cytogenetic evidence of gene amplification was found in two cell lines; as an hsr(11)(q 13) in one and as dmins in the other. The clonal karyotypes of four cell lines were compared with those of their respective primary tumors. In all cell lines, clonal evolution had occurred, with loss of some rearrangements present in the primary tumors or the gain of additional abnormalities.     

Comparative cytogenetic study of spindle cell and pleomorphic leiomyosarcomas of soft tissues: a report from the CHAMP Study Group

Leiomyosarcomas (LMS) of soft tissues frequently show complex karyotypic changes, and no specific aberration has been identified. The aim of this study was to search for recurrent chromosome aberrations in soft tissue LMSs and to correlate these, if present, with morphological and clinical parameters. From a series of soft tissue sarcomas thoroughly reexamined cytogenetically and histopathologically, 45 LMSs were retrieved; 35 were classified microscopically as spindle cell, 3 as epithelioid, and 7 as pleomorphic. Clonal chromosome changes were present in 14, 3, and 3 cases, respectively. This series was combined with 11 previously published, karyotypically abnormal pleomorphic LMSs for cytogenetic-clinico-histopathological correlations. The breakpoints were widely scattered, with no predilection of any of the recurrent breakpoints and losses to any of the morphologic subtypes. Combining numerical and unbalanced structural changes, the most frequently lost segments were 3p21-p23 (11 cases), 8p21-pter, 13q12-q13, 13q32-qter (10 cases each), 1q42-qter, 2p15-pter, 18p11 (9 cases each), 1p36, 11q23-qter (8 cases each), and 10q23-qter (7 cases). The most frequent gain was 1q12-q31 (6 cases). There was a greater frequency of losses in 1p and 8p and a lower frequency of losses in 10q and 13q in tumors that had metastasized than in localized tumors. We conclude that LMSs with clonal abnormalities display highly complex karyotypic changes and extensive heterogeneity. No significant correlation exists between these changes and age and sex of the patients, or with depth of tumor, topography, microscopic subtype, or tumor grade. Losses in 1p36 and 8p21-pter may be associated with increased risk of metastases. Comparison of our findings in soft tissue LMS with those previously reported in LMS in other locations suggest that the karyotypic profile is more dependent on site of origin than on microscopic features.     

Karyotypic evolution in acute myelomonocytic leukemia with pericentric inversion of chromosome 16

A 37-year-old Japanese male patient with acute myelomonocytic leukemia subtype M4 (according to FAB classification) associated with bone marrow eosinophilia and specific chromosome abnormalities: a pericentric inversion of chromosome 16, inv(16)(p13q22); a long arm deletion of chromosome #7, del(7)(q22q34); and a gain of chromosomes #8 and #22 is reported. In addition to the modal karyotype, 47,XY,7q-,inv(16),+22, there were three other clones whose karyotypes were 46,XY,inv(16); 47,XY,inv(16),+22; and 48,XY,+8,inv(16),+22. As these karyotypes were related to each other, the presence of multiple clones indicated that karyotypic evolution had occurred. The karyotypic evolution associated with 7q- has not been reported previously in patients with M4Eo with inv(16).     

Multiple cytogenetic abnormalities in a case of osteosarcoma

Cytogenetic analysis of a highly malignant osteosarcoma in a 17-year-old girl revealed extremely complex karyotypic changes with several different clonal numerical and structural chromosome aberrations. The composite karyotype was interpreted as 39–41,X,t(X;9)(q11;p24), −1,der(1),−4,−4,−5,i(7q),−8,del(8)(q21),t(10;19)(p13;q13),del(11)(p11p13),t(12;18)(q24;q12), −13,13q+,−14,14p+,−15,15q+,17p+,19q+,−21,+22,+3–6 mar.     

Reconstruction of the ancestral karyotype of eutherian mammals

Applying the parsimony principle, i.e. that chromosomes identical in species belonging to different taxa were likely to be present in their common ancestor, the ancestral karyotype of eutherian mammals (about 100 million years old) was tentatively reconstructed. Comparing chromosome banding with all ZOO-FISH data from literature or studied by us, this reconstruction can be proposed with only limited uncertainties. This karyotype comprised 50 chromosomes of which 40–42 were acrocentrics. Ten ancestral pairs of chromosomes were homologous to a single human chromosome: 5, 6, 9, 11, 13, 17, 18, 20, X and Y (human nomenclature). Nine others were homologous to a part of a human chromosome: 1p+q (proximal), 1q, 2p+q (proximal), 2q, part of 7, 8q, 10p, 10q and 19p (human nomenclature). Finally, seven pairs of chromosomes, homologs to human chromosomes 3 + 21, 4 + 8p, part of 7 + 16p, part of 12 + part of 22 (twice), 14+15, 16q+19q, formed syntenies disrupted in man. This revised version was published online in July 2006 with corrections to the Cover Date.     

Shwachman syndrome as mutator phenotype responsible for myeloid dysplasia/neoplasia through karyotype instability and chromosomes 7 and 20 anomalies

An investigation of 14 patients with Shwachman syndrome (SS), using standard and molecular cytogenetic methods and molecular genetic techniques, showed that (1) the i(7)(q10) is not, or not always, an isochromosome but may arise from a more complex mechanism, retaining part of the short arm; (2) the i(7)(q10) has no preferential parental origin; (3) clonal chromosome changes, such as chromosome 7 anomalies and del(20)(q11), may be present in the bone marrow (BM) for a long time without progressing to myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML); (4) the del(20)(q11) involves the minimal region of deletion typical of MDS/AML; (5) the rate of chromosome breaks is not significantly higher than in controls, from which it is concluded that SS should not be considered a breakage syndrome; (6) a specific kind of karyotype instability is present in SS, with chromosome changes possibly found in single cells or small clones, often affecting chromosomes 7 and 20, in the BM. Hence, we have confirmed our previous hypothesis that the SS mutation itself implies a mutator effect that is responsible for MDS/AML through these specific chromosome anomalies. This conclusion supports the practice of including cytogenetic monitoring in the follow-up of SS patients.     

Genome wide copy number abnormalities in pediatric medulloblastomas as assessed by array comparative genome hybridization

Array-based comparative genomic hybridization was used to characterize 22 medulloblastomas in order to precisely define genetic alterations in these malignant childhood brain tumors. The 17p(-)/17q(+) copy number abnormality (CNA), consistent with the formation of isochromosome 17q, was the most common event (8/22). Amplifications in this series included MYCL, MYCN and MYC previously implicated in medulloblastoma pathogenesis, as well as novel amplicons on chromosomes 2, 4, 11 and 12. Losses involving chromosomes 1, 2, 8, 10, 11, 16 and 19 and gains of chromosomes 4, 7, 8, 9 and 18 were seen in greater than 20% of tumors in this series. A homozygous deletion in 11p15 defines the minimal region of loss on this chromosome arm. In order to map the minimal regions involved in losses, gains and amplifications, we combined aCGH data from this series with that of two others obtained using the same RPCI BAC arrays. As a result of this combined analysis of 72 samples, we have defined specific regions on chromosomes 1, 8p, 10q, 11p and 16q which are frequently involved in CNAs in medulloblastomas. Using high density oligonucleotide expression arrays, candidate genes were identified within these consistently involved regions in a subset of the tumors.     

Complex karyotypic anomalies, including an i(5p) marker chromosome, in malignant mixed mesodermal tumor of the ovary

Cytogenetic analysis of short-term cultures initiated from an ovarian malignant mixed mesodermal tumor yielded the following karyotype: 59-61, XX,t(1;?)(p36;?), +t(1;9) (q43;q21), +t(2;?)(p25;?), +i(5p), +i(5p), +7, +t(7;?)(p13;?), +8,der(11) (pter----cen----q23::q13----q23::q13----q23::?), +12, + der(13)t(13;15)(q21;q15), -15,der(16) (16qter----cen----16p13::hsr::8q21----8qter), +19, + der(20)t(X;20)(q13;p13), -22, +4 - 6mar. Because the only other cytogenetically characterized ovarian neoplasm of this rare histopathologic subtype also had a small metacentric marker interpreted as an isochromosome for the short arm of a B-group chromosome, we suggest that i(5p) constitutes a nonrandom anomaly in mixed mesodermal tumors.     

Loss of the chromosomal region 5q11-q31 in the myeloid cell line HL-60: Characterization by comparative genomic hybridization and fluorescence in situ hybridization

Comparative genomic hybridization was used to identify the regions of genomic gain and loss in the myeloid cell line HL-60. These included amplification at 8q24 corresponding to previous reports of overrepresentation of the MYC gene; loss of material from the short arms of chromosomes 9 (9p21-p23), 10, and 17; loss of the chromosome regions 9q32-qter and 14q11-q24; and an extra copy of chromosome 18. Additionally, deletion of the 5q11-q31 region was noted and was associated with translocation of chromosome 5 material to chromosomes 16 and a dic(5;17)(q11;p11) chromosome (previously described as mar3). Loss of chromosome 5 material in myeloid malignancies, including the M2 subtype from which HL-60 was derived, is usually associated with interstitial deletions of the long arm, including the critical 5q31 region, resulting in a 5q-chromosome. The HL-60 cell line may be a useful model to investigate the role of potential tumour suppressor genes associated with loss of 5q material in myeloid leukaemias. Genes Chromosom Cancer 15:182–186 (1996). © 1996 Wiley-Liss, Inc.     

Cytogenetic studies of a human medullary thyroid carcinoma cell line

Detailed karyotypic analyses were performed on early and late passages of the TT cell line derived from malignant cells of a patient with the sporadic form of medullary thyroid carcinoma. Most of the cells examined were hypodiploid with a modal chromosome number of 43. The cells have a complex karyotype with ten rearranged chromosomes found in early passages and 12 rearranged chromosomes in late passages. The karyotypic pattern was relatively stable with continued in vitro culture, and consistent alterations involved chromosomes X, #1, #3, #5, #7, #8, #9, #10, #11, #12, and #14. Rearrangements of chromosome #11 are of particular interest, because the gene for calcitonin, the polypeptide hormone marker for medullary thyroid carcinoma resides on this chromosome. In early passages, one #11 contained an insertion within band q13, and this abnormality was retained in late passages. In late passage cells the other #11 homolog developed a deletion of part of the short arm, which involves the calcitonin gene region. We were unable to detect any deletion of chromosome band 20p12, previously reported by other investigators to occur in the germ line of patients with the hereditary form of medullary thyroid carcinoma.