Characterization of nonrandom chromosomal gains and losses in multiple myeloma by comparative genomic hybridization

Clonal chromosomal changes in multiple myeloma (MM) and related disorders are not well defined, mainly due to the low in vivo and in vitro mitotic index of plasma cells. This difficulty can be overcome by using comparative genomic hybridization (CGH), a DNA-based technique that gives information about chromosomal copy number changes in tumors. We have performed CGH on 25 cases of MM, 4 cases of monoclonal gammopathy of uncertain significance, and 1 case of Waldenstrom's macroglobulinemia. G-banding analysis of the same group of patients demonstrated clonal chromosomal changes in only 13 (43%), whereas by CGH, the number of cases with clonal chromosomal gains and losses increased to 21 (70%). The most common recurrent changes detected by CGH were gain of chromosome 19 or 19p and complete or partial deletions of chromosome 13. +19, an anomaly that has so far not been detected as primary or recurrent change by G-banding analysis of these tumors, was noted in 2 cases as a unique change. Other recurrent changes included gains of 9q, 11q, 12q, 15q, 17q, and 22q and losses of 6q and 16q. We have been able to narrow the commonly deleted regions on 6q and 13q to bands 6q21 and 13q14-21. Gain of 11q and deletion of 13q, which have previously been associated with poor outcome, can thus be detected by CGH, allowing the use of this technique for prognostic evaluation of patients, without relying on the success of conventional cytogenetic analysis.     

Characterization of Y3 receptor-mediated synaptic inhibition by chimeric neuropeptide Y-peptide YY peptides in the rat brainstem

Archival material from primary and metastatic renal clear cell carcinomas of 25 patients was studied by comparative genomic hybridization. Copy number changes of entire chromosomes or chromosomal subregions were detected in 22 primary and 21 metastatic tumors. Copy number changes affected the following chromosomes in at least 20% of the 25 primary tumors (minimal common region given in parentheses): gains were noted for chromosomes 1 (1q21-->q23), 5 (5q31-->q34), 7 (7p), 8 (8q), 16 (16p), 17 (17q12-->qter), 19, and 22 (22q12-->qter); losses were revealed for chromosomes 3 (3p21-->pter), 8 (8p23-->pter), 14(14q21-->qter), and Y. The same chromosomal regions that were involved in primary renal clear cell carcinomas were also found in the respective metastatic tumors but with strikingly different frequencies for a few regions. Metastatic tumors showed a significantly higher frequency of complete or partial gains of the long arm of chromosome 1, in particular at 1q21-->q23 than primary tumors (16 cases versus 6 cases; P < 0.005). These data suggest a correlation of metastatic events in renal clear cell carcinomas with an increase in the copy number of genes located at 1q, in particular at 1q21-->q23. In contrast, the entire or partial loss of the short arm of chromosome 3 was significantly less frequent in metastatic tumors (8 cases versus 15 cases; P < 0.025). The validity of 1q and 3p copy number changes detected by comparative genomic hybridization was confirmed by interphase cytogenetics with region-specific yeast artificial chromosomes to paraffin-embedded tumor tissue sections.     

Comparison of benign and malignant follicular thyroid tumours by comparative genomic hybridization

DNA copy number changes were compared in 29 histologically benign follicular adenomas, of which five were atypical, and 13 follicular carcinomas of the thyroid by comparative genomic hybridization. DNA copy number changes were frequent in adenomas (14 out of 29, 48%). Most changes were gains, and they always involved a gain of the entire chromosome 7 (10 out of 29, 34%); other common gains involved chromosomes 5 (28%), 9 (10%), 12 (24%), 14 (21%), 17 (17%), 18 (14%) and X (17%). Losses were found only in four (14%) adenomas. Two of the five atypical adenomas had DNA copy number losses, and none had gains. Unlike adenomas, gains were rare and losses were frequent in carcinomas. A loss of chromosome 22 or 22q was particularly common in carcinomas (6 out of 13, 46%), whereas a loss of chromosome 22 was found in only two (7%) adenomas, one of which was atypical (P = 0.002). A loss of 1p was also frequent in carcinomas (31%), but gains of chromosomes 5, 7, 12, 14 or X that were common in adenomas were not found. Loss of chromosome 22 or 22q was present in six of the eight widely invasive follicular carcinomas, but in only one of the five minimally invasive carcinomas. We conclude that large DNA copy number changes are common in thyroid adenomas. These changes are strikingly different from those found in follicular carcinomas consisting of few losses and frequent gains, especially those of chromosome 7. A loss of chromosome 22 is common in widely invasive follicular carcinoma.     

Cytogenetic analysis of 52 colorectal carcinomas--non-random aberration pattern and correlation with pathologic parameters

Cytogenetic analysis of short-term cultures from 52 colorectal carcinomas revealed a normal karyotype in 13 and clonal chromosome aberrations in 39 tumors. In the abnormal group, 13 tumors had simple numerical changes only, whereas 26 had at least one structural rearrangement with or without concomitant numerical changes. The most common numerical abnormalities were, in order of decreasing frequency, +7, -18, -Y, +8, +13 and -14. The most common structural rearrangements affected, again in order of decreasing frequency, chromosomes 8, 1, 6, 7, 17, 3, 11, 13, 14, 16, 2 and 10. The chromosome bands most frequently involved in the structural changes were 8q10, 17p11, 11q13, 8p11, 6q21, 7p15, 7q36, 12q13, 13q10, and 16q13. The most frequent genomic imbalances brought about by the structural rearrangements were losses from chromosome arms 8p, 1p, 6q, 17p, 7p, and 16q, as well as gains of 7q, 8q, 13q, and 11q. A statistically significant (p < 0.05) correlation between the karyotypic pattern and tumor grade was found, with the poorly differentiated carcinomas generally having more massive chromosomal abnormalities.     

Comparative genomic hybridization in childhood acute lymphoblastic leukemia

DNA copy number changes were studied by comparative genomic hybridization (CGH) on bone marrow samples obtained from 72 patients with childhood acute lymphoblastic leukemia (ALL) at diagnosis. The patients had been admitted to the Helsinki University Central Hospital (Finland) between 1982 and 1997. CGH showed DNA copy number changes in 45 patients (62.5%) with a mean of 4.6 aberrations per patient (range, 1 to 22). The results of CGH and chromosome banding analysis were generally concordant, but CGH facilitated specific karyotyping in 34 cases. DNA copy number gains were more frequent than losses (gains:losses, 6:1). Gains of DNA sequences affected almost exclusively whole chromosomes and were most commonly observed in chromosomes 21 (25%), 18 (22.2%), X (19.4%), 10 (19.4%) and 17 (19.4%). The most common partial gain was 1q31-q32 (8.3%). The most common gains of chromosomes 21, 18, X, 10, 17, 14, 4, 6 and 8 appeared concurrently. High-level amplifications of small chromosome regions were sporadic, detected only in two patients (2.8%). Chromosome 21 was involved in both cases. The most common losses were 9p22-pter (12.5%) and 12p13-pter (11.1%). No statistically significant association between the CGH findings and the diagnostic white blood cell count was observed.     

Recurrent gains of 1q, 8 and 12 in the Ewing family of tumours by comparative genomic hybridization

Comparative genomic hybridization (CGH) was used to detect copy number changes of DNA sequences in the Ewing family of tumours (ET). We analysed 20 samples from 17 patients. Fifteen tumours (75%) showed copy number changes. Gains of DNA sequences were much more frequent than losses, the majority of the gains affecting whole chromosomes or whole chromosome arms. Recurrent findings included copy number increases for chromosomes 8 (seven out of 20 samples; 35%), 1q (five samples; 25%) and 12 (five samples; 25%). The minimal common regions of these gains were the whole chromosomes 8 and 12, and 1q21-22. High-level amplifications affected 8q13-24, 1q and 1q21-22, each once. Southern blot analysis of the specimen with high-level amplification at 1q21-22 showed an amplification of FLG and SPRR3, both mapped to this region. All cases with a gain of chromosome 12 simultaneously showed a gain of chromosome 8. Comparison of CGH findings with cytogenetic analysis of the same tumours and previous cytogenetic reports of ET showed, in general, concordant results. In conclusion, our findings confirm that secondary changes, which may have prognostic significance in ET, are trisomy 8, trisomy 12 and a gain of DNA sequences in 1q.     

Multiple genetic aberrations including evidence of chromosome 11q13 rearrangement detected in pituitary adenomas by comparative genomic hybridization

OBJECT: This study was conducted to determine whether comparative genomic hybridization (CGH) is a more sensitive method for detecting genetic aberrations than other tests currently in use. METHODS: The authors used CGH to examine 40 primary and 13 recurrent adenomas obtained from 52 patients for loss and gain of genetic material. Copy number aberrations (CNAs) were detected in 25 (48%) of the 52 patients studied. The chromosomes affected were, in order of decreasing frequency, 11, 7, X, 1, 8, 13, 5, 14, 2, 6, 9, 10, 12, 3, 18, 21, 4, 16, 15, 19, 22, and Y. Endocrinologically active adenomas were more likely to contain (p = 0.009) and had a greater number (p = 0.003) of CNAs. Of 26 adenomas with CNAs, 18 showed multiple aberrations involving entire chromosomes or chromosome arms. The most frequent CNA involving a chromosome subregion, which was present in four (8%) of 53 adenomas, was the loss of all chromosome 11 material except for a preserved common segment containing 11q13. Immunoperoxidase staining did not detect cyclin D1 expression in those four cases, making cyclin D1 an unlikely target of this rearrangement. CONCLUSIONS: These findings indicate that genetic abnormalities are present in pituitary adenomas at a higher rate than previously reported, are associated with endocrinological activity, and often involve several chromosomes. Rearrangement at 11q13 may inactivate a tumor suppressor gene or activate an oncogene that is important in the initiation or progression of sporadic pituitary adenomas.     

Comparative genomic hybridization and loss of heterozygosity analyses identify a common region of deletion at 15q11.1-15 in human malignant mesothelioma

Comparative genomic hybridization analysis was performed to identify chromosomal imbalances in 24 human malignant mesothelioma (MM) cell lines derived from untreated primary tumors. Chromosomal losses accounted for the majority of genomic imbalances. The most frequent underrepresented segments were 22q (58%) and 15q1.1-21 (54%); other recurrent sites of chromosomal loss included 1p12-22 (42%), 13q12-14 (42%), 14q24-qter (42%), 6q25-qter (38%), and 9p21 (38%). The most commonly overrepresented segment was 5p (54%). DNA sequence amplification at 3p12-13 was observed in two cases. Whereas some of the regions of copy number decreases (i.e., segments in 1p, 6q, 9p, and 22q) have previously been shown to be common sites of karyotypic and allelic loss in MM, our comparative genomic hybridization analyses identified a new recurrent site of chromosomal loss within 15q in this malignancy. To more precisely map the region of 15q deletion, loss of heterozygosity analyses were performed with a panel of polymorphic microsatellite markers distributed along 15q, which defined a minimal region of chromosomal loss at 15q11.1-15. The identification of frequent losses of a discrete segment in 15q suggests that this region harbors a putative tumor suppressor gene whose loss/inactivation may contribute to the pathogenesis of many MMs.     

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.     

The new toothpastes

Total genomic DNA sampled from 20 oral squamous cell carcinomas (SCCs) and from four SCC cell lines, was examined for genomic imbalances using comparative genomic hybridisation (CGH). Gains and losses of DNA copy number aberrations (CNAs) were found in the primary tumours, but also in the cell lines at a varying number. The patterns of CNAs proved to be rather peculiar in oral SCCs, gains of genetic material clearly dominating compared with losses, and a rather high uniformity of these patterns was an impressive finding. Hypersomies of whole chromosomes, e.g. numbers 17 and 19 or of whole chromosome arms, e.g. 20q, were particularly evident. The segments most frequently gained in oral SCCs were 3q26-q27, 5p15 and 9q34 (16 of 20 tumours each), as well as 1p36.3, 8q24, 10q26, 19 and 20q (15/20 each). Among the 15 tumours with more than 10 CNAs, all showed these imbalances. 11q13 was a band often involved in increases (14/20 tumours), but in several tumours was involved in amplification of DNA copy number. Several other chromosomal segments over represented in more than 60% of the tumours, as, for example, 12q24, 15q22-q24, 16p13.2 and 17q (14/20 tumours each), 6q26-qter, 7p22, 12p12.2-p13, 14q31-q32.2 (13/20) and 1q32-q41, 2q37, 16q23-q24 (12/20 each). In contrast, loss of material affected only a few chromosomal segments, as, for example, 3p12 (12 of the 20 tumours), 5q21 (10/20), 6q13 (8/20). The peculiarities of these findings, in some respect, differ from those found in other epithelial tumours, suggesting a high impact of environmental factors in the generation and progression of these tumours.     

Frequent gains on chromosome arms 1q and/or 8q in human endometrial cancer

Comparative genomic hybridization (CGH) was employed to survey genomic regions with increased and decreased copy number of the DNA sequence in 15 endometrial cancers [10 cases with microsatellite instability positive (MI+) and 5 cases with MI-]. Twelve of these 15 tumors (80%) showed abnormalities in copy number at one or more of the chromosomal regions. There were no regions with frequent chromosomal losses. Conversely, 11 of 15 cases (73%) showed gains on chromosome arms 1q (8/15; 53%) and/or 8q (6/15; 40%). Concordant gains of both chromosome arms 1q and 8q were observed in all three endometrial cancers of histological grade 3. These results suggest that these two chromosomal regions may contain genes whose increased expression contributes to development and/or progression of endometrial carcinogenesis. Two cases were further analyzed by fluorescence in situ hybridization (FISH) using three probes on chromosome 1 and two probes on chromosome 8 to more accurately determine increases in copy number. We found gains of chromosome 1q to 2.9-3.6 copies per cell and on 8q to 4.4 copies per cell.     

Amplification of DNA sequences from chromosome 19q13.1 in human pancreatic cell lines

Conventional cytogenetics and comparative genomic hybridization (CGH) were utilized to identify recurrent chromosomal imbalances in 12 pancreatic adenocarcinoma cell lines. Multiple deletions and gains were observed in all cell lines. Losses affecting chromosomes or chromosome arms 9p, 13, 18q, 8p, 4, and 10p and gains involving chromosome arms or bands 19q13.1, 20q, 5p, 7p, 11q, 3q25-qter, 8q24, and 10q were commonly observed. Interestingly, 19 distinct sites of high-level amplification were found by CGH. Recurrent sites involved 19q13.1 (6 cases), 5p (3 cases), and 12p and 16p (2 cases). Amplification of KRAS2 was demonstrated in 2 cell lines and that of ERBB2 in another. To define the occurrence of chromosome 19 amplification further, two-dimensional analysis of NotI genomic restriction digests and fluorescence in situ hybridization using probes from band 19q13.1 were utilized. High-level amplification of overlapping sets of chromosome 19 NotI fragments was exhibited in 3 cell lines of which 2 showed amplification of both OZF and AKT2 genes and 1 that of AKT2 alone. In these 3 cell lines, amplification of chromosome 19 sequences was associated with the presence of a homogeneously staining region. Our results provide evidence of heterogeneity in the extent of chromosome 19 amplification and suggest the existence of yet unknown amplified genes that may play a role in pancreatic carcinogenesis.     

Bronchial mucosal immunoreactivity of sensory neuropeptides in severe airway diseases

DNA copy number changes were investigated in 29 leiomyosarcomas by comparative genomic hybridization. The most frequent losses were detected in 10q (20 cases, 69%) and 13q (17 cases, 59%). The most frequent gains were detected in 17p (16 cases, 55%). The most frequent high-level amplifications were detected in 17p (7 cases, 24%) and 8q (6 cases, 21%). A total of 137 losses and 204 gains were detected. Small tumors (less than 5 cm in diameter) displayed fewer changes per sample (3 to 11; mean, 7) than the other tumors (4 to 22; mean, 13). There was an increase in the number of gains from small tumors (mean, 4) to very large tumors (>20 cm; mean, 10). However, the number of losses was similar in small, large, and very large tumors (mean, 4.5). Tumor size-related aberrations were observed. Gains in 16p were detected in all small tumors but were infrequent in large and very large tumors (27% and 11%, respectively). Similarly, gains and high-level amplifications in 17p were more common in small (80%) than in very large tumors (33%). Gains in 1q, 5p, 6q, and 8q were not seen in any of the small tumors but were detected in large and very large tumors. Gains in 6q and 8q occurred in 8 of 9 cases (89%) of very large tumors, 5 of them with a high-level amplification in 8q.     

Recurrent DNA copy number changes in 1q, 4q, 6q, 9p, 13q, 14q and 22q detected by comparative genomic hybridization in malignant mesothelioma

Comparative genomic hybridization (CGH) analyses were performed on 27 human pleural mesothelioma tumour specimens, consisting of 18 frozen tumours and nine paraffin-embedded tumours, to screen for gains and losses of DNA sequences. Copy number changes were detected in 15 of the 27 specimens with a range from one to eight per specimen. On average, more losses than gains of genetic material were observed. The loss of DNA sequences occurred most commonly in the short arm of chromosome 9 (p21-pter), in 60% of the abnormal specimens. Other losses among the abnormal specimens were frequently detected in the long arms of chromosomes 4 (q31.1-qter, 20%), 6 (q22-q24, 33%), 13 (33%),14 (q24-qter, 33%) and 22 (q13, 20%). A gain in DNA sequences was found in the long arm of chromosome 1 (cen-qter) in 33% of the abnormal specimens. Our analysis is the first genome-wide screening for gains and losses of DNA sequences using comparative genomic hybridization in malignant pleural mesothelioma tumours. The recurrent DNA sequence changes detected in this study suggest that the corresponding chromosomal areas most probably contain genes important for the initiation and progression of mesothelioma.     

Chromosomal gains and losses in uveal melanomas detected by comparative genomic hybridization

Eleven uveal melanomas were analyzed using comparative genomic hybridization (CGH). The most abundant genetic changes were loss of chromosome 3, overrepresentation of 6p, loss of 6q, and multiplication of 8q. The smallest overrepresented regions on 6p and 8q were 6pter-->p21 and 8q24-->qter, respectively. Several additional gains and losses of chromosome segments were repeatedly observed, the most frequent one being loss of 9p (three cases). Monosomy 3 appeared to be a marker for ciliary body involvement. CGH data were compared with the results of chromosome banding. Some alterations, e.g., gains of 6p and losses of 6q, were observed with higher frequencies after CGH, while others, e.g., 9p deletions, were detected only by CGH. The data suggest some similarities of cytogenetic alterations between cutaneous and uveal melanoma. In particular, the 9p deletions are of interest due to recent reports about the location of a putative tumor-suppressor gene for cutaneous malignant melanoma in this region.     

Cytogenetic studies of epithelial ovarian carcinoma

We performed cytogenetic studies of 36 human epithelial ovarian carcinomas using in situ culture and robotic harvest. We obtained analyzable metaphases of all 36 tumors (100%). One or more chromosomally abnormal clones were observed in 80% of tumors. Common clonal chromosome gains (each occurring in six or more cases) included +1, +2, +3, +6, +7, +9, and +12. Common clonal chromosome losses (occurring in 12 or more cases) included -X, -4, -8, -11, -13, -15, -17, and -22. Common clonal structural abnormalities (occurring in four or more cases) involved regions 1p36, 1q32, 1q42, 3p13-->p26, 3q26-->q29, 7p22, 9q34, 11p13-p15, 17q21-->q23, 19p13.3, and 19q13.3. Trisomy 12 was noted as the sole anomaly in three of five borderline and grade 1 tumors. Two grade 2 tumors contained i(1q), -14, -15 and -22. The results suggest that the pathogenesis of borderline and low-grade tumors may differ from that of higher grade tumors. Two high-grade tumors had an apparent translocation between 17q21 and 19p13.3, two chromosome regions believed to be critical to ovarian carcinogenesis.     

Analysis of genomic alterations in benign, atypical, and anaplastic meningiomas: toward a genetic model of meningioma progression

Nineteen benign [World Health Organization (WHO) grade I; MI], 21 atypical (WHO grade II; MII), and 19 anaplastic (WHO grade III; MIII) sporadic meningiomas were screened for chromosomal imbalances by comparative genomic hybridization (CGH). These data were supplemented by molecular genetic analyses of selected chromosomal regions and genes. With increasing malignancy grade, a marked accumulation of genomic aberrations was observed; i.e., the numbers (mean +/- SEM) of total alterations detected per tumor were 2.9 +/- 0.7 for MI, 9.2 +/- 1.2 for MII, and 13.3 +/- 1.9 for MIII. The most frequent alteration detected in MI was loss on 22q (58%). In MII, aberrations most commonly identified were losses on 1p (76%), 22q (71%), 14q (43%), 18q (43%), 10 (38%), and 6q (33%), as well as gains on 20q (48%), 12q (43%), 15q (43%), 1q (33%), 9q (33%), and 17q (33%). In MIII, most of these alterations were found at similar frequencies. However, an increase in losses on 6q (53%), 10 (68%), and 14q (63%) was observed. In addition, 32% of MIII demonstrated loss on 9p. Homozygous deletions in the CDKN2A gene at 9p21 were found in 4 of 16 MIII (25%). Highly amplified DNA sequences were mapped to 12q13-q15 by CGH in 1 MII. Southern blot analysis of this tumor revealed amplification of CDK4 and MDM2. By CGH, DNA sequences from 17q were found to be amplified in 1 MII and 8 MIII, involving 17q23 in all cases. Despite the high frequency of chromosomal aberrations in the MII and MIII investigated, none of these tumors showed mutations in exons 5-8 of the TP53 gene. On the basis of the most common aberrations identified in the various malignancy grades, a model for the genomic alterations associated with meningioma progression is proposed.     

Mapping of chromosomal imbalances in pancreatic carcinoma by comparative genomic hybridization

To identify recurrent chromosomal imbalances in pancreatic adenocarcinoma, 27 tumors were analyzed by using comparative genomic hybridization. In 23 cases chromosomal imbalances were found. Gains of chromosomal material were much more frequent than losses. The most common overrepresentations were observed on chromosomes 16p (eight cases), 20q (seven cases), 22q (six cases), and 17q (five cases) and under-representations on a subregion of chromosome 9p (eight cases). Distinct high-level amplifications were found on 1p32-p34, 6q24, 7q22, 12p13, and 22q. These data provide evidence for a number of new cytogenetically defined recurrent aberrations which are characteristic of pancreatic carcinoma. The overrepresented or underrepresented chromosomal regions represent candidate regions for potential oncogenes and tumor suppressor genes, respectively, possibly involved in pancreatic tumorigenesis.     

Effect of regeneration and hyperplasia on levels of DNA base oxidation in rat liver

Clonal chromosome aberrations identified after short-term culture are presented for 13 chondrosarcomas; in 5 cases both the primary tumors and local recurrences were studied. The stemline chromosome number was hypodiploid or hyperhaploid in 9 tumors. The most frequent numerical anomalies were, in falling order of frequency, loss of chromosomes Y, 10, 13, and 6, and gain of chromosomes 7 and 20. No recurrent structural rearrangement was found, but chromosome bands 5q13, 1q21, 7p11, and 20q11 were each involved in three different rearrangements. Karyotypic heterogeneity was assessed in two different ways: as the presence of more than one clone in one sample and as the presence of different clones in different samples from the same surgical specimen. Clonal karyotypic evolution was demonstrated in 6 of the 7 cases in which two or more samples could be investigated. All 6 showed intersample heterogeneity. Intrasample heterogeneity was found in only 5 of the 28 samples with aberrations. By comparing the incidences of the nonrandomly occurring aberrations in stemlines and sidelines in the heterogeneous tumors, it was possible to conclude that loss of chromosome 13 and rearrangement of band 5q13 were early events in the clonal evolution.