Genomic imbalances and patterns of karyotypic variability in mantle-cell lymphoma cell lines

Mantle-cell lymphoma (MCL) is genetically characterized by 11q13 chromosomal translocations involving the CCND1 gene. We have characterized five MCL cell lines, JVM-2, GRANTA-519, REC-1, JEKO-1, and NCEB-1, combining metaphase and array comparative genomic hybridization, multicolor-FISH, and molecular analysis. Our results revealed common gained regions at 2p14, 9q31.2-qter, 11q13.1-q21, 13q14-q21.2, 13q34-qter and 18q21.1-q22.1, and losses at 1p21.2-p31.1, 2p11.2, 8p21.2-pter, 9p21.3-pter, 11q23.3-qter, 17p11.2-pter, and 17q21.2-q22.2. All cell lines except JVM-2, displayed moderate or high numerical chromosome instability. In addition, an ongoing level of chromosome rearrangements was observed in REC-1. Surprisingly, NCEB-1 carried several stable mouse chromosomes and showed expression of both human and murine bcl-2 protein. Our findings indicate that these cell lines represent three patterns of chromosome evolution in MCL and may be useful to understand the pathogenesis of this neoplasm.     

Clonal chromosome abnormalities in tumor cells from patients with sporadic renal cell carcinomas

The karyotype of 75 sporadic, nonpapillary renal cell carcinomas was analyzed using chromosome banding techniques. Sixty-five tumors had near-diploid stemlines, and ten had near-triploid or near-tetraploid stemlines. Aberration of chromosome 3 was detected in 71 cases. The nonrandom changes on chromosome 3 were monosomy 3, terminal deletions, or unbalanced translocations; the 3p13-pter segment was identified as the minimal common deletion. The rearrangement of chromosome 3p was the only karyotype change in 13 tumors. Abnormalities of chromosome 5 resulting in trisomy for the 5q22-qter region were found in 36 cases, while the loss of 14q22-qter segment was observed in 34 tumors. Trisomy for chromosome 7 was detected in 17 cases, and monosomy 8 and 9 occurred 14 times each. Our data show that more than one specific chromosomal site may be involved in the development of human renal cell carcinomas.     

Tissue-specific expression of a constitutional 3;6 translocation: development of multiple bilateral renal-cell carcinomas

We describe a German family carrying a constitutional translocation (3;6) (p13;q25.1) in 3 consecutive generations. The only member of the family over 50 years of age and carrying the translocation developed multiple bilateral renal-cell carcinomas. We performed chromosome analysis of 4 out of 5 primary tumours, which were characterized by different clonal karyotypes. The constitutionally translocated 3p13-pter segment was lost with or without the receptor chromosome 6 in each tumour. Additional karyotypic changes were trisomy 5, 7 and 18, monosomy 14 and 21, and loss of the Y chromosome, all karyotype changes occurring frequently in sporadic non-papillary RCCs. This case is discussed with regard to the possible role of suppressor gene inactivation by constitutional translocation in the development of familial renal cancers.     

Cytogenetic and molecular findings in 75 clear cell renal cell carcinomas

Cytogenetic analysis of 75 clear cell renal cell carcinomas (RCC) from adult patients revealed abnormal karyotypes in 59 (79%) tumors. Among structural abnormalities, the most frequent were deletions and unbalanced translocations leading to loss of 3p (found in 68% of karyotypically abnormal tumors), followed by rearrangements of chromosomes 5 (in 37%) and 1 (in 20%). Fifteen unbalanced interchromosomal rearrangements and one reciprocal translocation have not been hitherto reported in clear cell RCC. The most common numerical aberrations were trisomy 7, seen in 44% of tumors, and loss of chromosome Y, detected in 48% of RCCs diagnosed in male patients. In 25 tumors, loss of heterozygosity (LOH) analysis was performed using five polymorphic markers spanning region 3p13-p25. LOH was identified in 10 RCCs with 3p loss detected cytogenetically and 4 karyotypically aberrant tumors without cytogenetic rearrangements of 3p; no LOH was found in 3 tumors with 3p loss seen at the cytogenetic level. Overall, 3p loss was detected by cytogenetic and/or LOH analyses in 75% of RCCs with abnormal karyotype studied. The presence or absence of 3p loss did not correlate with tumor size, nodal involvement, tumor grade or its ability to metastasize. However, karyotypes of metastasizing tumors contained more aberrations than those of non-metastasizing RCCs (5.5 versus 2.9 aberrations per tumor, respectively), and -14/14q-, -17 and -10 were significantly more frequent in metastasizing tumors, suggesting that these aberrations might contribute to the progression of RCC. One patient had t(X;1)(p11.2;p34) as a sole abnormality in the stemline. This is the sixth case with this translocation reported to date. Together with our case, all but 1 RCC with t(X;1)(p11.2;p34) had morphology with a clear cell component, which contrasts these RCCs from tumors harboring t(X;1)(p11.2;q21) that largely had papillary morphology.     

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 8q 10, 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, 1 p, 6q, 17p, 7p, and 16q, as well as gains of 7q, 8q, 13q, and 11 q. 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.     

Karyotypic characterization of bronchial large cell carcinomas

Cytogenetic analysis of short-term cultures from 26 primary bronchial large cell carcinomas and 1 metastasis from a primary large cell carcinoma revealed clonal chromosome abnormalities in 20 tumors and a normal karyotype in 6. No outgrowth was obtained in 1 case. Simple aberrations were present in 3 tumors; in 1, the only change was a reciprocal translocation between chromosomes 1 and 6, in another the sole anomaly was a supernumerary marker ring chromosome and in a third loss of the Y chromosome was the only clonal change. The remaining 17 tumors had complex karyotypes. The chromosomes most frequently involved in structural rearrangements were chromosomes 1, 2, 3, 5, 6, 7, 6, 10, 11, 13, 14 and 17. The bands most frequently affected were 1q11-12, 1p13. 7q11, and 17p11-13. The rearrangements led to repeated losses of 1p, 1q, 3p, 6q, 7q and 17p and gains of 5q and 7p. The emerging karyotypic picture of large cell lung carcinomas indicates more similarities with adenocarcinomas than with other pathologic subgroups of lung cancer. © 1994 Wiley-Liss, Inc.     

Cytogenetic findings in malignant peripheral nerve sheath tumors

Clonal chromosome aberrations were detected in 8 short-term cultured malignant peripheral nerve sheath tumors (MPNST). Seven had a near-triploid chromosome number and I was in the hyperhaploid-hypodiploid range. No recurrent structural rearrangements were found; the bands most frequently involved (3 tumors) were 7p11, 12p13 and 14q11. The most common numerical changes were loss of a sex chromosome (all tumors) and loss of at least 1 copy of chromosomes 8, 16 and 22 (4 tumors). Pooling our data with those on the 20 previously published MPNST with abnormal karyotypes, we found that the chromosome number has often been in the triploid range (12 tumors), with stem line variation between 34 and 270. All chromosome arms, except 22p and the Y chromosome, were involved in recombinations. The most frequently rearranged bands were 7p22 (6 tumors) and 1p21, 7p11 and 14q11 (5 tumors each). Most numerical and unbalanced structural aberrations have led to loss of genetic material, in particular from Xq26-qter (13 tumors); 11q22-qter and 13p (12 tumors); 9p22-pter, 11p13-pter, 17p and 17q11-21 (11 tumors); 1p22-32 and 1p34-pter (10 tumors) and 6q25-qter and chromosome 16 (9 tumors). © 1995 Wiley-Liss, Inc.     

Shared cytogenetic abnormalities in lung-tumors and corresponding peripheral-blood lymphocytes

We analyzed chromosomal alterations in primary lung tumours and peripheral blood lymphocytes (PBLs) from 10 lung cancer patients (nine with non-small cell lung carcinoma and one with small cell lung carcinoma) to determine whether there were shared chromosomal changes in the normal and diseased tissue of these cases. This study revealed that each paired sample had at least three chromosomes and two chromosomal regions in common for structural rearrangements. The chromosomes most frequently found structurally altered in paired analysis were 1 and 3 (60% each), 5 (50%), 6, 7, and 9 (40% each), and 14 (30%). Chromosome region 3p13-3p21 was structurally rearranged in both the normal and tumour tissues of three patients. Chromosome 3 was structurally rearranged in all ten tumours. The chromosome arms most commonly affected in the tumours were 3p (nine times), 9p and 5q (eight times each), Ip and 7q (six times each), 10q and 11q (five times each), 14q and 6q (four times each). The most frequently affected chromosomal regions in these tumours were (in decreasing order) 9p23-p24, 3p21-3p13, 5q11, 1p34, 7q22, and 11q13. Frequent polysomy of 7 and 12 and loss of D-group chromosomes were also observed in the tumours analyzed. Comparing the changes found only in tumours with those found in both PBLs and tumours was helpful in shedding some light on the probable sequence of genetic events leading to lung cancer. This investigation also offered compelling evidence that genomic instability at the chromosomal level in PBLs corresponds with the genetic changes observed in tumours indicating that PBL analysis can help identify the early chromosomal changes in lung cancer. PBL chromosomal analysis thus has a promising future in the genetic analysis of lung cancers.     

Karyotypic characterization of papillary thyroid carcinomas.

BACKGROUND: Cytogenetic studies performed in papillary thyroid carcinoma (PTC) identified chromosome 10q rearrangements with breakpoints at 10q11.2 as the most frequent aberrations in these tumors. In the current study, the authors aimed to identify other chromosomal abnormalities nonrandomly associated with papillary thyroid carcinomas. METHODS: Cytogenetic analysis was performed on 94 papillary thyroid carcinomas after short-term culture of the tumors sterile fragments. RESULTS: Clonal chromosomal changes were found in 37 tumors (40%). Structural cytogenetic abnormalities were observed in 18 carcinomas. Chromosomes 1, 3, 7, and 10 were the most frequently involved in rearrangements. Pooled results of the breakpoints detected in these tumors, as well as those described in the literature, allowed the authors to verify as the most common breakpoint loci 1p32-36, 1p11-13, 1q, 3p25-26, 7q34-36, and 10q11.2. The correlation between the karyotype features of the 94 PTCs and the histologic data revealed that some PTC follicular variants were characterized by chromosomal aberrations commonly found in thyroid follicular adenomas: a del(11)(q13q13), a t(2;3)(q13;p35), and gains of chromosomes 3, 5, 7, 9, 12, 14, 17, and 20. In the tall cell PTC variant group, 4 of the 7 tumors presented clonal cytogenetic changes, 3 (75%) of which were characterized by anomalies of chromosome 2 that lead to a overrepresentation of the long arm of this chromosome. Noted also in these series was an association between complex karyotypes and tumors with poorly differentiated histiotypes. CONCLUSIONS: In this study, the authors report chromosome 1p32-36, 1p11-13, 3p25-26, and 7q32-36 as novel breakpoint cluster regions in PTC, and they suggest that there are cytogenetic changes preferentially associated with the follicular and tall cell PTC variants.     

Chromosomal changes during development and progression of prostate adenocarcinomas

Chromosomal copy number changes were investigated in 16 prostate carcinomas, 12 prostatic intraepithelial neoplasias (PIN; 4 low-grade and 8 high-grade) adjacent to the invasive tumour areas, and 5 regional lymph node metastases. For this purpose, comparative genomic hybridization (CGH) was performed and a copy number karyotype for each histomorphological entity was created. CGH on microdissected cells from non-neoplastic glands was carried out on 3 different cases to demonstrate the reliability of the overall procedure. None of the non-neoplastic tissue samples revealed chromosome copy number changes. In PIN areas, chromosomal imbalances were detected on chromosomes 7, 8q, Xq (gains), and on 4q, 5q, 8p, 13q and 18q (losses). In the primary tumours, recurrent (at least 25% of cases) gains on chromosomes 12q and 15q, and losses on 2q, 4q, 5q, Xq, 13q and 18q became apparent. Losses on 8p and 6q as well as gains on 8q and of chromosome 7 were also detected at lower frequencies than previously reported. The pooled CGH data from the primary carcinomas revealed a novel region of chromosomal loss on 4q which is also frequently affected in other tumour entities like oesophageal adenocarcinomas and is supposed to harbour a new tumour suppressor gene. Gains on chromosome 9q and of chromosome 16 and loss on chromosome 13q were observed as common aberrations in metastases and primary tumours. These CGH results indicate an accumulation of chromosomal imbalances during the PIN-carcinoma-metastasis sequence and an early origin of tumour-specific aberrations in PIN areas.     

Karyotypic features of malignant tumors of the nasal cavity and paranasal sinuses

Cytogenetic analysis of short-term cultures from 6 tumors of the nasal cavity and paranasal sinuses—one esthesioneuroblas-toma, 2 adenocarcinomas and 3 squamous-cell carcinomas (SCC)—revealed clonal chromosome aberrations in all cases. The esthesioneuroblastoma had a complex hyperdiploid karyotype. None of the aberrations was similar to those previously described in short-term cultures or established cell lines from esthesioneuroblastomas. The 2 adenocarcinomas had complex karyotypic changes, which in both cases included rearrangements of bands 9p22 and 14q11. One SCC had 5 unrelated pseudodiploid clones, I displayed a highly complex karyotype, including rearrangement of band 11 q 13, and I had simple karyotypic changes with loss of 6q material and gain of 3q. These findings are similar to those described in head-and-neck SCC at other sites.     

Frequency and pattern of karyotypic abnormalities in human prostate cancer

The cytogenetic evaluation of 30 cultured primary prostatic cancer specimens obtained during radical prostatectomies of patients with relatively early stage disease is reported. The majority of specimens examined showed a normal male karyotype, 46,XY. Nine samples contained clonally abnormal populations including five specimens which were hyperdiploid (modal range, 65-92 chromosomes), one specimen containing double minute chromosomes, and three containing structural aberrations. Loss of the Y chromosome and a partial trisomy for chromosome 4 was observed in a sample from one patient. Another sample showed a translocation between the long arms of chromosomes 5 and 7. The only tumor obtained from a previously irradiated patient contained no normal cells, a modal chromosome number of 45, loss of chromosomes 2 and Y, and multiple structural rearrangements. The appearance of any clonal cytogenetic abnormality correlated in general with a poorly differentiated state of cancer. A survey of all available previous cytogenetic data on human prostate adenocarcinoma indicated that the loss of chromosomes 1, 2, 5, and Y, the gain of chromosomes 7, 14, 20, and 22, and rearrangements involving chromosome arms 2p, 7q, and 10q are the most common changes observed. This suggests that, although the assignment of a single chromosomal aberration as a marker for early stage prostatic cancer is unlikely, several consistent "hotspots" might be of significance in the etiology of this disease.     

The utility of spectral karyotyping in the cytogenetic analysis of newly diagnosed pediatric acute lymphoblastic leukemia.

We applied multicolor spectral karyotyping (SKY) to a panel of 29 newly diagnosed pediatric pre B-cell ALLs with normal and abnormal G-banded karyotypes to identify cryptic translocations and define complex chromosomal rearrangements. By this method, it was possible to define all add chromosomes in six cases, a cryptic t(12;21)(p13;q11) translocation in six cases, marker chromosomes in two cases and refine the misidentified aberrations by G-banding in two cases. In addition, we identified five novel non-recurrent translocations - t(2;9)(p11.2;p13), t(2;22) (p11.2;q11.2), t(6;8)(p12;p11), t(12;14)(p13;q32) and t(X;8)(p22.3;q?). Of these translocations, t(2;9), t(2;22) and t(12;14) were identified by G-banding analysis and confirmed by SKY. We characterized a t(12;14)( p13;q32) translocation by FISH, and identified a fusion of TEL with IGH for the first time in ALL. We identified a rearrangement of PAX5 locus in a case with t(2;9)(p11.2;p13) by FISH and defined the breakpoint telomeric to PAX5 in der(9)t(3;9)(?;p13). These studies demonstrate the utility of using SKY in combination with G-banding and FISH to augment the precision with which chromosomal aberrations may be identified in tumor cells.     

Histopathologic subtype-specific genomic profiles of renal cell carcinomas identified by high-resolution whole-genome single nucleotide polymorphism array analysis

To elucidate the novel and common genetic changes in histopathologic subtype-specific profiles of renal cell carcinomas (RCCs), a newly developed high-resolution whole-genome array analysis was applied. Human CNV370-Duo DNA Analysis BeadChip (genotype 370K) was used in a panel of 22 primary clear cell RCCs (ccRCCs), seven papillary RCCs (PRCCs) (six type II and one type I) and eight chromophobe RCCs (ChRCCs). In ccRCC, a chromosome 3p loss was identified in 95% of the carcinomas, suggesting that 3p loss is the first stage in ccRCC carcinogenesis. Other frequent changes included losses of 1p (23%), 3q (46%) and 8p (32%), and gains of 5q (32%), 7p (27%), 7q (27%) and 1q (23%). The most frequent chromosomal losses in PRCC (43%) were noted in 3p and 3q, followed by 29% of losses of 1p, 1q, 11q, 18q, 22p and 22q, and gains of 20q (57%), 20p (43%), 8q (43%) and 12q (43%). Loss of the entire chromosomes 1, 2, 6, 8, 10, 13 or 17 was noted in patients with ChRCC. A high-density single nucleotide polymorphism array analysis confirmed that partial chromosomal changes rarely occur in ChRCC. Additionally, 32 microdeletions and 10 microamplifications of less than 1 Mb were detected, which may represent potential candidate tumor suppressor genes and oncogenes, respectively.     

Prognostic impacts of cytogenetic findings in clear cell renal cell carcinoma: gain of 5q31-qter predicts a distinct clinical phenotype with favorable prognosis.

To evaluate the prognostic significance of cytogenetic findings in clear cell renal cell carcinoma (RCC), cytogenetic results of 118 primary RCCs were evaluated in relation to classical indicators of prognosis and overall survival. Losses in 3p (98.3%) were most prevalent and included 32 (27.6%) monosomies of chromosome 3 and 84 (72.4%) structural aberrations involving 3p, of which 36 were unbalanced translocations, der(3)t(3;5)(p11-p22;q13-q31), resulting in duplication of 5q sequences. Patients with gain of 5q31-qter resulting from either polysomies or structural rearrangements of 5q, the most frequent of which was der(3)t(3;5), had a significantly better outcome than those without this aberration (P = 0.001). There was no association between gain of 5q or der(3)t(3;5) and any of the well-known variables for prognosis, including low versus high clinical stage and grade of malignancy. Among additional chromosomal aberrations, loss of chromosome 9/9p was associated with distant metastasis at diagnosis (P = 0.006). The data indicate that gain of 5q identifies a clinically favorable cytogenetic variant of clear cell RCC and demonstrate the impact of specific chromosome aberrations as additional prognostic indicators in clear cell RCC.     

Small-cell lung cancer is characterized by a high incidence of deletions on chromosomes 3p, 4q, 5q, 10q, 13q and 17p.

The genetic mechanisms that define the malignant behaviour of small-cell lung cancer (SCLC) are poorly understood. We performed comparative genomic hybridization (CGH) on 22 autoptic SCLCs to screen the tumour genome for genomic imbalances. DNA loss of chromosome 3p was a basic alteration that occurred in all tumours. Additionally, deletions were observed on chromosome 10q in 94% of tumours and on chromosomes 4q, 5q, 13q and 17p in 86% of tumours. DNA loss was confirmed by loss of heterozygosity (LOH) analysis for chromosomes 3p, 5q and 10q. Simultaneous mutations of these six most abundant genetic changes were found in 12 cases. One single tumour carried at least five deletions. DNA under-representations were observed less frequently on chromosome 15q (55%) and chromosome 16q (45%). The prevalent imbalances were clearly indicated by the superposition of the 22 tumours to a CGH superkaryogram. In our view, the high incidence of chromosomal loss is an indication that SCLC is defined by a pattern of deletions and that the inactivation of multiple growth-inhibitory pathways contributes in particular to the aggressive phenotype of that type of tumour.     

Comparative genomic hybridization analysis detected frequent overrepresentation of chromosome 3q in squamous cell carcinoma of the lung

The aim of this study was to provide cytogenetic data about squamous cell carcinomas of the lung and to evaluate their characteristic alterations and histogenetic relations. We analyzed 41 squamous cell lung carcinomas by comparative genomic hybridization (CGH) technique. CGH was performed using directly fluorochrome-conjugated DNA. Chromosomal regions where the mean ratio fell below 0.75 were therefore considered to reflect DNA copy number loss (underrepresentation), whereas regions where the mean ratio exceeded 1.25 were considered gains (overrepresentations) in the tumor genome. Overrepresentations were considered to be high-level amplification when the fluorescence ratio exceeded 1.5. Chromosomal imbalances were observed in every case. Copy number gains frequently were detected at 3q, 5p, 8q, 12p, and Xq. Losses were found at 16p, 4q, 5q, 3p, 17p, and 16q. DNA amplifications were observed at 12 regions: 3q26.1-27, 8q13-23.1, 12p12.3-pter, 12q15, 2p14-16, 4q28-31.2, 5p13.1-pter, 6q21-22.3, 7p11.2-13, 13q21.2-32, 18p11.2-pter, and 20p11.2-pter. Gains on 3q were frequently detected not only in the more than 3 cm group (79%) but also in the 3 cm or less group (77%). The mean frequency of gained or lost chromosomal regions was 7.2+/-4.7 in the 3 cm or less group (n=13) and 10.2+/-6.3 in the more than 3 cm group (n=28) (P=0.4503). The mean frequency of gained or lost chromosomal regions was significantly higher in the carcinoma with lymph node metastasis group (12.5+/-7.6 regions) (n=12) than in the carcinoma without lymph node metastasis group (7.9+/-4.6) (n=29) (P=0.0251). In conclusion, an increased copy number at 3q may contribute to the development of squamous cell carcinoma of the lung.     

Array comparative genomic hybridization reveals distinct DNA copy number differences between gastrointestinal stromal tumors and leiomyosarcomas

Leiomyosarcomas are spindle cell tumors showing smooth muscle differentiation. Until recently, most gastrointestinal stromal tumors (GIST) were also classified as smooth muscle tumors, but now GISTs are recognized as a separate entity, defined as spindle cell and/or epithelioid tumors localized in the gastrointestinal tract. Using microarray-based comparative genomic hybridization (array CGH), we have created a detailed map of DNA copy number changes for 7 GISTs and 12 leiomyosarcomas. Considerable gains and losses of chromosomal segments were observed in both tumor types. The most frequent aberration observed in GISTs was loss of chromosomes 14 and 22, with minimal recurrent regions in 14q11.2-q32.33 (71% of the tumors) and 22q12.2-q13.31 (100%). In leiomyosarcomas, frequent loss of chromosome 10 and 13q was observed, with minimal recurrent regions in 10q21.3 (75%) and 13q14.2-q14.3 (75%). Recurrent high-level amplification of 17p13.1-p11.2 was detected in leiomyosarcomas. Expression profiling using cDNA microarrays revealed four candidate genes in this region with high expression (AURKB, SREBF1, MFAP4, and FLJ10847). Altered expression of AURKB and SREBF1 has been observed previously in other malignancies. Hierarchical clustering of all samples separated GISTs and leiomyosarcomas into two distinct clusters. Statistical analysis identified six chromosomal regions, 1p36.11-p13.1, 9q21.11-9q34.3, 14q11.2-q23.2, 14q31.3-q32.33, 15q24.3-q26.3, and 22q11.21-q13.31, which were significantly different in copy number between GISTs and leiomyosarcomas. Our results show the potential of using array comparative genomic hybridization to classify histologically similar tumors such as GISTs and leiomyosarcomas.     

Cytogenetic findings in 14 benign cartilaginous neoplasms

Benign cartilaginous tumors represent a spectrum of neoplastic processes with variable clinical and pathologic presentations. These tumors are histologically characterized by the presence of chondrocytes surrounded by a cartilaginous matrix. Few studies describe karyotypic abnormalities in these benign lesions. We report a series of 14 chondromas from a single institution. Conventional cytogenetics was performed on short term cultures from all cases. Clonal chromosome aberrations were found in nine tumors. One soft tissue chondroma contained three clones with t(6;12)(q12;p11.2), t(3;7)(q13;p12), and der(2)t(2;18)(p11.2;q11.2). Three periosteal chondromas displayed random structural aberrations of chromosomes 2, 3, 6, 7, and 11 and loss of chromosome 13. Among the enchondromas, three tumors displayed chromosome losses, one contained a complex translocation involving chromosomes 12, 15, and 21 as well as an inv(2)(p21q31),t(12;15;21)(q13;q14;q22) and a separate enchondroma showed a translocation involving chromosomes 12 and 22. Our data suggest that considerable cytogenetic heterogeneity exists among benign chondromatous tumors.