Analysis of cytogenetic alterations in stage III serous ovarian adenocarcinoma reveals a heterogeneous group regarding survival, surgical outcome, and substage

Ovarian cancer is the leading cause of death among patients with gynecological cancers, but the biology of these tumors is still among the least understood of all major human malignancies. In this study, comparative genomic hybridization was used to determine chromosomal alterations in 98 stage III serous papillary adenocarcinomas. The tumors were grouped according to survival and the main prognostic factors stage and surgical outcome. There were chromosomal imbalances that were significantly more common in tumors from patients who died than in tumors from patients who survived: gains of 1q24-qter and losses of 4p, 4q31.1-qter, 5q12-q22, 8p, 16q, and X. Furthermore, we observed that gains of 8q23-8q24.2 and losses of 4p, 4q13-4q26, 4q31.1-qter, 5q12-q22, 8p, and 16q were significantly more common in tumors from patients with macroscopic residual tumor after primary surgery, compared to tumors from those who had undergone radical surgery. Gains of 3q13.3-qter, 6p, 7q21-q31, and 11q13-q23 and losses of 4q31.1-qter and 16q were more common in stage IIIc tumors than in stage IIIa+b tumors. On the basis of our results, we suggest that there are biological differences among the groups mentioned above and that absence of chromosomal aberrations in specific regions predicts a good clinical outcome for individual patients.     

Genomic imbalances in Korean hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most prevalent gastrointestinal malignant tumors in Southeast Asia. Thirty-one cirrhotic HCC, 14 noncirrhotic HCC, and 13 metastastic HCC in the Korean population were investigated on microdissected tissues for chromosomal aberrations by degenerate oligonucleotide-primed polymerase chain reaction (PCR) comparative genomic hybridization. A number of prominent sites of genomic imbalances were observed. The gains of 1q, 6p, 7, 8q, 12q, 13q3-q32, 16p, 17q, and 20q and the losses of 1p, 4q, 6q, 8p, 9p, and 13q regions were observed with a similar high frequency in all types. Various chromosomal aberrations were observed preferentially to specific types. Gains of 4p15-pter, 10q24-qter, 18p11-pter, and 19p10-pter and a loss of 11q14-q22 were observed in the cirrhotic HCC, whereas losses of 14q21-q23 and 10q22-q23 were observed in noncirrhotic HCC. In metastatic HCC, gains of 3q25-qter and Xp21-pter and losses of 21q11-qter and Y were observed. The recurrent gains and losses of chromosomal regions identified in this study are consistent with several previous observations and provide possible candidate regions for the involvement of tumorigenesis and progressions of HCC.     

Analysis of genetic alterations in salivary gland tumors by comparative genomic hybridization.

In order to define and map chromosomal copy number alterations in salivary gland tumors (SGTs), a comparative genomic hybridization (CGH) technique was applied to two pleomorphic adenomas (PAs), one adenoid cystic carcinoma (ACC), and one basal cell adenocarcinoma (BCAC). The PAs exhibited regional copy number losses at 5q12.4-q14.1, 9q12-q21.13, and 16q11.2, as well as a gain at 20p12.1; among these, the losses at the 9q12-q21.11 and 16q11.2 regions were common to both PAs. The ACC showed overrepresentations of the entire regions of chromosomes 16 and 20, a regional gain at 22q12.3-q13.1, and no losses. In the BCAC, regional gains at 9p21.1-pter, 18q21.1-q22.3, and 22q11.23-q13.31 as well as losses at 2q24.2 and 4q25-q27 were seen; the gain at 22q12.3-q13.1 was common in both the ACC and the BCAC. These CGH data indicate that different genetic alterations are present in the different types of SGTs, and that the alterations involve several chromosomes. The discovery of common alterations in the same and/or different types of tumors might be important in the understanding of the development and progression of the SGTs.     

Comparative genomic hybridization reveals complex genetic changes in primary breast cancer tumors and their cell lines

DNA copy number changes were characterized by comparative genomic hybridization (CGH) in 18 breast cancer cell lines. In 5 of these, the results were comparable with those from the primary tumors of which the cell lines were established. All of the cell lines showed extensive DNA copy number changes, with a mean of 16.3 +/- 1.1 aberrations per sample (range 7-26). All of the cell lines had a gain at 8q22-qter. Other common gains of DNA sequences occurred at 1q31-32 (89%), 20q12-q13.2 (83%), 8q13 (72%), 3q26.1-qter (67%), 17q21-qter (67%) 5p14 (61%), 6p22 (56%), and 22pter-qter (50%). High-level amplifications were observed in all cell lines; the most frequent minimal common regions were 8q24.1 (89%), 20q12 (61%), 1q41 (39%), and 20p11.2 (28%). Losses were observed less frequently than gains and the minimal common regions of the most frequent losses were Xq11-q12 (56%), Xp11.2-pter (50%), 13q21 (50%), 8p12-pter (44%), 4p13-p14 (39%), 6q15-q22 (39%), and 18q11.2-qter (33%). Although the cell lines showed more DNA copy number changes than the primary tumors, all aberrations, except one found in a primary tumor, were always present in the corresponding cell line. High-level amplifications found both in primary tumors and cell lines were at 1q, 8q, 17q, and 20q. The DNA copy number changes detected in these cell lines can be valuable in investigation of tumor progression in vitro and for a more detailed mapping and isolation of genes implicated in breast cancer.     

Gains of 12q are the most frequent genomic imbalances in adult fibrosarcoma and are correlated with a poor outcome

Comparative genomic hybridization was used to analyze 41 adult fibrosarcomas from 34 patients. Thirty-one patients showed in their tumors DNA sequence copy number changes (mean 11, range 3-25). The minimal common regions for the most frequent gains were narrowed down to 12q21 (18 cases); 12q14-q15 and 14q22 (16 cases each); 4q22, 7q31, and 14q23-q24 (15 cases each); and 4q21, 4q23-q24, 8q22, and 12q22 (14 cases each). Twenty-five high-level amplifications were observed in 12 samples. 12q21 and 18p were affected three times each; and 1p21, 4q31.3, 7p21, 12q14-q15, Xp22.1-p22.2, and Xq22-q23 two times each. Losses were less frequent than gains. Early stages of adult fibrosarcomas were characterized by frequent gains of chromosomes 2, 4q, and 14q, whereas gains of chromosomes 7 and 8q were associated with progression. Gains of 12q were frequent in all of the developmental steps of this soft-tissue sarcoma. By investigation of several tumors of the same patient, a number of corresponding changes were always detected. Adult fibrosarcomas from patients who died during the observation time showed statistically significant more frequent gains of 8q, 12q, 13q, and 15q compared to the fibrosarcomas of patients who are alive. Gains and high-level amplifications of 12q14-q22, which were the most frequent genomic imbalances, partly reflected an MDM2 amplification, indicating the importance of this region in the tumorigenesis of sarcomas. In adult fibrosarcomas, a gain of 12q22 correlated significantly (P = 0.028) with a poor overall survival rate.     

Do DNA copy number changes differentiate uterine from non-uterine leiomyosarcomas and predict metastasis?

DNA copy number changes were investigated in 51 (19 uterine and 32 nonuterine) primary leiomyosarcomas by comparative genomic hybridization. The aim was to evaluate whether true biological differences exist between uterine and nonuterine leiomyosarcoma and whether changes revealed by comparative genomic hybridization have prognostic value. Genomic imbalances were found in 48 (94%) cases. The most frequent DNA copy number changes were losses in 10q (35%), 13q (57%), and 16q (41%), gains in 1q (41%), and gains and high-level amplifications in 17p (39%). Gains were nearly as frequent as losses in both uterine and nonuterine leiomyosarcoma. Correlation-based tree modeling revealed two clusters that segregated significantly a group of uterine (gains at 1q11-q24) and a group of nonuterine (losses at 13q14-q34, 16q11.1-q24, and 10q21-q26) cases. The nonuterine cluster was associated with subcutaneous origin and a trend toward increased metastasis-free survival. Further explorative analyses identified aberrations associated with shorter metastasis-free survival time, including losses at 2q32.1-q37 and gains at 8q24.1-q24.3, whereas the cases with losses at 6cen-p25 showed longer metastasis-free survival time.     

Frequent amplification and rearrangement of chromosomal bands 6p12-p21 and 17p11.2 in osteosarcoma

Osteosarcoma (OS) is a highly malignant bone neoplasm of children and young adults. It is characterized by chaotic karyotypes with complex marker chromosomes. We applied a combination of molecular cytogenetic techniques including comparative genomic hybridization (CGH), spectral karyotyping (SKY), and fluorescence in situ hybridization (FISH) to decipher the chromosomal complexity in a panel of 25 tumors. Combined SKY and G-banding analysis identified several novel recurrent breakpoint clusters and 9 nonrecurrent reciprocal translocations. CGH identified several recurrent chromosomal losses including 2q, 3p, 9, 10p, 12q, 13q, 14q, 15q, 16, 17p, and 18q, gains including Xp, Xq, 5q, 6p, 8q, 17p, and 20q, and high-level chromosomal amplifications at Xp11.2, 1q21-q22, 4p11, 4q12, 5p15, 6p12.1, 8q13, 8q23, 10q11, 10q22, 11q13, 11q23, 12q13-q14, 13q21-q34, 16q22, 17p11.2, 17q21-q22, 18q22, 20p11.2, and 20q12. Frequent amplification and rearrangement involving chromosomal bands at 6p12-p21 and 17p11.2 were found in 28% and 32% of cases, respectively. In an attempt to identify the genes involved in these amplicons, we used three nonoverlapping BAC clones contained within each amplicon as probes for FISH analysis, leading to a more detailed characterization and quantification of the 6p and 17p amplicons.     

DNA Copy Number Changes in Development and Progression in Leiomyosarcomas of Soft Tissues

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.     

Genomic alterations in uterine leiomyosarcomas: potential markers for clinical diagnosis and prognosis

Genomic alterations were analyzed in 21 uterine leiomyosarcomas (ULMSs) by comparative genomic hybridization. DNA copy number changes were detected in all 21 tumors. The most frequent losses were 13q (16/21 = 76%), 10q (13/21 = 62%), 16q (8/21 = 38%), 12p (7/21 = 33%), and 2p (9/21 = 43%). The most common gains were 17p (8/21 = 38%), Xp (7/21 = 33%), and 1q (7/21 = 33%). High-copy-number gains (ratio > 1.5) were identified in Xp, 1q, and 17p. Loss of 13q was identified in both low-grade and high-grade tumors. Inactivation of a tumor suppressor gene in 13q may be an early event in the development of leiomyosarcomas. Loss of 10q, 2p, and 12p and gains of 1q as well as 17p were frequently found in high-grade tumors and recurrent tumors. Inactivation of tumor suppressor genes and activation of oncogenes in these regions may be associated with a more aggressive behavior of ULMS. Patients with only loss of 13q and without the other alterations listed above had longer survival times. Gains of Xp, 17p, and 1q and losses of 13q, 10q, 16q, 12p, and 2p have been reported in extra-uterine leiomyosarcomas. Our findings indicate that the pathogenesis of uterine leiomyosarcomas and extra-uterine leiomyosarcomas follows the same genetic pathways.     

Loss of chromosome 13 is the most frequent genomic imbalance in malignant fibrous histiocytomas. A comparative genomic hybridization analysis of a series of 30 cases.

Regional chromosome localizations of DNA copy number imbalances were studied by comparative genomic hybridization in 30 malignant fibrous histiocytomas: 13 primary tumors (2 myxoid, 9 storiform pleomorphic, and 2 with more undifferentiated phenotype) and 17 local recurrences (2 myxoid, 11 storiform pleomorphic, and 4 with more undifferentiated phenotype). Abnormal comparative genomic hybridization (CGH) profiles were observed in 25 tumors (83%). The most frequent gains (ratio > 1.2) corresponded, by order of frequency, to entire Xp, and bands 1q21, 19q13.1, 19p13, 5p13-p14, 1p31, 17p, 18p, 20q, 1p35, 17q23, and 22q12. High levels of gains (ratio > 1.5) were recurrently detected for Xp (10 cases), and in bands 1q21-q22 (8 cases), 3q27 (4 cases), 5p13-p14 (3 cases), 13q32-q34 (3 cases), 15q22-q26 (3 cases), and 17p11-p12 (3 cases). Losses of 13q12-q14 or 13q21 were observed in a large proportion of tumors (17 cases), suggesting that a gene localized in this region could act as a tumor suppressor gene. Losses of 11q23, 2q32, 11p13, 10p, 1q4, 9p2, 16q12, 4q3, 10q25, 3p23, 2p24, and 12p were also recurrently observed. Taken together, these results provide an overview of chromosome imbalances present in MFH, which could be of use for diagnostic purposes. They point to various chromosome regions which may harbor genes important for malignant fibrous histiocytomas (MFH) oncogenesis and progression.     

Comparative genomic hybridization analysis reveals 3q gain resulting in genetic alteration in 3q in advanced oral squamous cell carcinoma.

We analyzed DNA sequence copy number aberrations (DSCNAs) in 17 primary oral squamous cell carcinomas (OSCCs) by comparative genomic hybridization. DSCNAs were detected frequently at 3q25-qter (7/17), Xp21 (5/17), and Xq12-q23 and 8q23-q24 (4/17), and losses were detected frequently at 13q21-q22 (5/17), 3p21-pter, 4p15-pter and 17p13 (4/17), and 8p22-pter and 9p21-pter (3/17). Four tumors showed amplifications of seven loci: 3q11-qter, 3q13, 3q26, 7q21-q22, 8q23-qter, 9p22-pter, and 12p11. The total number of DSCNAs was significantly greater in stage III and stage IV tumors than in stage I and stage II tumors (P=.008). Furthermore, 3q gain was detected preferentially in stage III and stage IV tumors (6/8) rather than in stage I and stage II tumors (1/9, P=.013). In our study, all tumors with gain of 3q also contained one or more loss(es) in common regions. On the other hand, all tumors with gain of 9p did not contain 3q gains. These observations indicate that gain of 3q and accumulation of DSCNAs are strongly associated with tumor progression in OSCC. Furthermore, 3q gain and loss of one or more additional loci in common aberration regions appears to be a group of DSCNs associated with dominant genetic pathways of leading to advanced OSCCs.     

Gains, losses, and amplifications of DNA sequences evaluated by comparative genomic hybridization in chondrosarcomas.

Comparative genomic hybridization was used to search for previously unknown gains and losses of DNA sequences along all chromosome arms in 29 chondrosarcoma specimens obtained from 23 patients. Extensive genetic aberrations, with a mean of 6 changes per tumor (range, 1 to 24), were detected in 21 of the 29 samples analyzed (72%). The majority of these changes were gains of whole chromosomes or whole chromosome arms. Gains of DNA sequence copy number were most frequent at 20q (38%), 17p (38%), 20p (31%), 1cen-q24 (28%), and 14q23-qter (28%). High-level amplifications of small chromosome regions were sporadic, detected in only 17% of the samples. The only recurrent high-level amplification, seen in two tumors (7%), affected the minimal common region 12cen-q15. Other amplifications, each encountered only once, involved 1p33-p35, 2p23-pter, 4p, 6p22-pter, 18q12-q22, 19p13.2, 19q13.2, and 20q13.1. Losses of DNA sequences were rare and were most commonly observed at 6cen-q22 (17%) and 9p (17%).     

Interphase fluorescence in situ hybridization detection of chromosome 17 and 17q region gains in neuroblastoma: are they secondary events?

Gains of chromosome 17 and 17q region are the most frequent chromosomal abnormalities in neuroblastoma and have been associated with established prognostic indicators. Interphase fluorescence in situ hybridization (FISH) was used to define the status of chromosome 17 in near-triploid (3n) and near-diploid/tetraploid (2n/4n) primary tumors. Gains of chromosome 17 and 17q were detected in 22 and 26 tumors, respectively, in which the ploidy status was determined mainly by the copy number of chromosome 1. Four different types of gains were detected: gain of whole chromosome 17 (+17) and three partial gains (17q11.2 approximately qter, 17q21.1 approximately qter, and 17q21.3 approximately qter). The 17q11.2 approximately qter gains were found in both the 2n/4n and the 3n tumors. Gains of 17q21.1 approximately qter and 17q21.3 approximately qter were found only in the 2n/4n group, and the latter was involved always as a der(22)t(17;22)(q21;q13). A high association was found between chromosome 17 gains and 3n ploidy: +17 was detected in 93% of the 3n group and was not observed in the 2n/4n group. The +17 clone or clones were always present in combination with a clone with normal copies of chromosome 17 and, in the majority, with a +17q11.2 approximately qter clone. We conclude that interphase FISH is a sensitive method for detecting whole and partial chromosome 17 gains in neuroblastoma and can demonstrate the simultaneous presence of several clones with different status of chromosome 17 in 3n neuroblastomas. We suggest that chromosome 17 and 17q gains are not a primary event in the development of neuroblastoma.     

Genomic imbalances in Schistosoma-associated and non-Schistosoma-associated bladder carcinoma. An array comparative genomic hybridization analysis

Carcinoma of the urinary bladder is the most common malignancy in many tropical and subtropical countries due to endemic infection by Schistosoma hematobium (bilharzia). In the current study, we performed a high-resolution analysis of gene copy number amplifications using array comparative genomic hybridization to compare DNA copy number changes in pools of Schistosoma-associated (SA) and non-Schistosoma-associated (NSA) bladder cancer (BC). Many DNA copy number changes were detected in all studies, with multiple gains and losses of genetic material. The most frequent alterations were gains on 5p15.2 approximately p15.33, 8q13.1, and 11q13, and losses on 8p21.3 approximately p22 and 22q13. Even when SA pools showed no Schistosoma-specific gene copy number profiling as compared to NSA pools, some genes seemed to be gained (ELN on 7q11.23) and some lost (PRKAG3 on 2q35 and PRDM6 on 5q23.2) in SA-SCC. The following genes were gained in all histopathologic categories: SRC (20q11.23), CEBPB (20q13.13), and GPR9 (Xq13.1). Our study did not provide clear evidence of differences in carcinogenesis of SA-BC and NSA-BC.     

Overrepresentation of the short arm of chromosome 12 in seminoma and nonseminoma groups of testicular germ cell tumors

Histopathological differentiation between dermatofibrosarcoma protuberans (DFSP) and dermatofibroma (DF) is often difficult, because both neoplasms share some clinical features and the presence of a storiform pattern. In the present study, we investigated the usefulness of comparative genomic hybridization (CGH) in the diagnosis of these entities by examining 12 DFSP and 12 DF cases. The most frequent DNA sequence copy number changes detected in 10 (83%) of 12 DFSP cases (mean, 1.9 aberrations/tumor; range, 0-3) consisted of gains of 17q22-qter (10 tumors), 22q13 (nine tumors), and 8q24.1-qter (three tumors). High-level amplification, which was detected in three tumors, was seen only in chromosome 17, with 17q23-q25 as the minimal common region. Loss of DNA sequences was not found in DFSP cases. In contrast, two (17%) of the 12 DF cases (mean, 0.5 aberrations/tumor; range, 0-4) showed DNA sequence copy number changes, although recurrent gains and losses and high-level amplifications were not observed. Gains were more common than losses in DF. Overrepresentation of 17q and 22q sequences was a common finding in DFSP but not in DF. Thus, CGH seems to be useful for distinguishing DFSP from DF in most cases.     

Comparison of chromosomal imbalances in neuroendocrine and non-small-cell lung carcinomas.

Lung carcinomas are represented by non-small-cell lung carcinomas (NSCLC) and neuroendocrine carcinomas (NE) which differ in their clinical presentation and prognosis. We used comparative genomic hybridization (CGH) to characterize and compare the chromosomal pattern of 11 NSCLC and 11 high-grade NE lung carcinomas. Overall, the total number of aberrations was higher in NSCLC than in high-grade NE lung tumors (p < 0.05) and gains predominated over losses in NSCLC (p < 0.0003). Gains common to both lung tumor phenotypes were detected in 1p, 1q, 3q, 5p, 6p, 8q, 12, 17q, 19p, 19q, 20p, 20q, and X, whereas common losses were found in 2q, 3p, 4p, 4q, 5q, 8p, 9p, 10p, 11p, 11q, 13q, and 17p. Major gains on 18q and losses on 2p and 16q were exclusively detected in high-grade NE lung tumors. On the other hand, major gains on 2p and 15q and losses on 21q were found only in NSCLC. Furthermore, gains within 22q11-q12 and 7p12-p15 were associated with NSCLC (p < 0.05). The differences in the pattern and distribution of genetic changes observed in NSCLC as opposed to high-grade NE lung carcinomas suggest the existence of distinct tumorigenic pathways between these two major classes of lung tumors.     

Low frequency of chromosomal imbalances in anaplastic ependymomas as detected by comparative genomic hybridization

We screened 26 ependymomas in 22 patients (7 WHO grade I, myxopapillary, myE; 6 WHO grade II, E; 13 WHO grade III, anaplastic, aE) using comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH). 25 out of 26 tumors showed chromosomal imbalances on CGH analysis. The chromosomal region most frequently affected by losses of genomic material clustered on 13q (9/26). 6/7 myE showed a loss on 13q14-q31. Other chromosomes affected by genomic losses were 6q (5/26), 4q (5/26), 10 (5/26), and 2q (4/26). The most consistent chromosomal abnormality in ependymomas so far reported, is monosomy 22 or structural abnormality 22q, identified in approximately one third of Giemsa-banded cases with abnormal karyotypes. Using FISH, loss or monosomy 22q was detected in small subpopulations of tumor cells in 36% of cases. The most frequent gains involved chromosome arms 17 (8/26), 9q (7/26), 20q (7/26), and 22q (6/26). Gains on 1q were found exclusively in pediatric ependymomas (5/10). Using FISH, MYCN proto-oncogene DNA amplifications mapped to 2p23-p24 were found in 2 spinal ependymomas of adults. On average, myE demonstrated 9.14, E 5.33, and aE 1.77 gains and/or losses on different chromosomes per tumor using CGH. Thus, and quite paradoxically, in ependymomas, a high frequency of imbalanced chromosomal regions as revealed by CGH does not indicate a high WHO grade of the tumor but is more frequent in grade I tumors.     

Cytogenetic analysis of myxoid liposarcoma and myxofibrosarcoma by array-based comparative genomic hybridisation

AIM: To investigate overall chromosomal alterations using array-based comparative genomic hybridisation (CGH) of myxoid liposarcomas (MLSs) and myxofibrosarcomas (MFSs). Materials and methods: Genomic DNA extracted from fresh-frozen tumour tissues was labelled with fluorochromes and then hybridised on to an array consisting of 1440 bacterial artificial chromosome clones representing regions throughout the entire human genome important in cytogenetics and oncology. RESULTS: DNA copy number aberrations (CNAs) were found in all the 8 MFSs, but no alterations were found in 7 (70%) of 10 MLSs. In MFSs, the most frequent CNAs were gains at 7p21.1-p22.1 and 12q15-q21.1 and a loss at 13q14.3-q34. The second most frequent CNAs were gains at 7q33-q35, 9q22.31-q22.33, 12p13.32-pter, 17q22-q23, Xp11.2 and Xq12 and losses at 10p13-p14, 10q25, 11p11-p14, 11q23.3-q25, 20p11-p12 and 21q22.13-q22.2, which were detected in 38% of the MFSs examined. In MLSs, only a few CNAs were found in two sarcomas with gains at 8p21.2-p23.3, 8q11.22-q12.2 and 8q23.1-q24.3, and in one with gains at 5p13.2-p14.3 and 5q11.2-5q35.2 and a loss at 21q22.2-qter. CONCLUSIONS: MFS has more frequent and diverse CNAs than MLS, which reinforces the hypothesis that MFS is genetically different from MLS. Out-array CGH analysis may also provide several entry points for the identification of candidate genes associated with oncogenesis and progression in MFS.     

DNA copy number amplifications in human neoplasms: review of comparative genomic hybridization studies.

This review summarizes reports of recurrent DNA sequence copy number amplifications in human neoplasms detected by comparative genomic hybridization. Some of the chromosomal areas with recurrent DNA copy number amplifications (amplicons) of 1p22-p31, 1p32-p36, 1q, 2p13-p16, 2p23-p25, 2q31-q33, 3q, 5p, 6p12-pter, 7p12-p13, 7q11.2, 7q21-q22, 8p11-p12, 8q, 11q13-q14, 12p, 12q13-q21, 13q14, 13q22-qter, 14q13-q21, 15q24-qter, 17p11.2-p12, 17q12-q21, 17q22-qter, 18q, 19p13.2-pter, 19cen-q13.3, 20p11.2-p12, 20q, Xp11.2-p21, and Xp11-q13 and genes therein are presented in more detail. The paper with more than 150 references and two tables can be accessed from our web site http://www.helsinki.fi/lglvwww/CMG.html. The data will be updated biannually until the year 2001.     

DNA copy number changes in epithelioid sarcoma and its variants: a comparative genomic hybridization study.

Epithelioid sarcoma is a distinctive, rare soft tissue sarcoma that typically involves the distal extremities in young adults, and shows epithelioid morphology and immunohistochemical markers of epithelial differentiation. The genetic background of epithelioid sarcoma is poorly understood, and knowledge of it could give insights into the pathogenesis of this tumor and its possible relationship with other malignant tumors. In this study, we analyzed DNA copy number changes in 30 epithelioid sarcomas by comparative genomic hybridization. DNA was extracted from microdissected samples of formaldehyde-fixed and paraffin-embedded tumors with a minimum of 60% of tumor cells in each sample. Sixteen tumors (53%) showed DNA copy number changes at one to six different genomic sites. The majority of the changes were gains, seen in 14 tumors, whereas 10 tumors showed losses. The most common recurrent gains were at 11q13 (five cases), 1q21-q23 (four cases), 6p21.3 (three cases), and 9q31-qter (three cases). High-level amplifications were detected once in 6p21.3-p21.1 and once in 9q32-qter. Recurrent losses were seen at 9pter-p23 (three cases), 13q22-q32 (three cases), 1p13-p22 (two cases), 3p12-p14 (two cases), 4q13-q33 (two cases), 9p21 (two cases), and 13q32-qter (two cases). The most common recurrent gain at 11q13 was seen in both classic cases and angiomatoid and rhabdoid variants supporting the relationship of these variants with the classic epithelioid sarcoma. Expression of cyclin D1 gene, located in 11q13, was immunohistochemically detected in nine of 15 cases including three of five cases with gain of 11q13, suggesting its involvement in epithelioid sarcoma. The observed comparative genomic hybridization changes give targets for future genetic studies on epithelioid sarcoma.