A comprehensive karyotypic analysis on Korean hepatocellular carcinoma cell lines by cross-species color banding and comparative genomic hybridization

Chromosomal aberrations were investigated in hepatitis B virus integrated into the hepatocellular carcinoma (HCC) cell lines SNU-368, SNU-449, SNU-398, SNU-182, and SNU-475 using Giemsa-banding, cross species color banding, and comparative genomic hybridization (CGH). The origins of the marker chromosomes were confirmed by fluorescence in situ hybridization with constructed chromosome painting probes. Each cell line had unique modal karyotypic characteristics and showed variable numbers of numerical and structural clonal cytogenetic aberrations. The gains were commonly detected on chromosome 1, and chromosome regions 6p, 7q, 8q, 10p, 17q, and 20; the losses were often found on 4q21 approximately qter, 13, 18q21 approximately qter, and Y. In particular, the breakpoints on 1p36, 1p13 approximately q21, 2p13 approximately q11, 6q10 approximately q11, 7q11, 7q22, 14q10, 16q10 approximately q13, 17q21, 18q21, and 19p11 approximately q11 were involved frequently at the multiple rearranged lesions. CGH analysis further confirmed the cytogenetic data, and the nonrandom rearrangements data suggested the candidate regions for the genes to be isolated which were related to HCC.     

Genomic rearrangements involving rDNA and centromeric heterochromatin in vulvar epidermoid carcinoma cell line A-431

The cytogenetic and molecular cytogenetic characterization of the human cell line A-431 derived from a vulvar epidermoid carcinoma is presented. A combination of karyotyping, fluorescence in situ hybridization (FISH) with chromosome- and/or region-specific probes, M-FISH, RxFISH, and comparative genomic hybridization (CGH) analysis was used. Six marker chromosomes with rearrangements involving insertions of single or double nucleolar organizing regions (NORs) and/or homogeneously staining regions containing active and overexpressed NORs and regions of centromeric heterochromatin were found: der(6), der(7), der(17), der(21), dic(13;14), and dic(14;18). The chromosomal origin of 14 other marker chromosomes was elucidated. Amplification of the C-MYC oncogene at 8q24 was revealed in two marker chromosomes: dup(8)(q24) and der(15)t(8;15)(q22;p11). Confirming previous reports, amplification of the cyclin D1 gene within an abnormal chromosome 11, that is, der(11)t(7;11)(p15;q21), was also detected. Loss of the TP53 tumor suppressor gene was evidenced over two der(17). Good concordance was found among karyotyping, FISH analysis, and CGH. Although reasons for NOR amplification or ectopic location in the epidermal carcinoma A-431 cell line are not clear yet, our data suggest that these phenomena play a supporting role with regard to other amplified genes. Thus, the A-431 cell line would be an appropriate model to study the different mechanisms involved in human tumorigenesis.     

Cytogenetic characterization and gene expression profiling of the trastuzumab-resistant breast cancer cell line JIMT-1

Resistance to the HER-2 targeting drug trastuzumab can be observed clinically, but the lack of suitable experimental models hampers studies of resistance mechanisms. We characterized a HER-2-positive carcinoma cell line (JIMT-1) derived from a 62-year-old breast cancer patient which was clinically resistant to trastuzumab. Multicolor fluorescence in situ hybridization revealed a complex hyperdiploid karyotype with numerous marker chromosomes and unbalanced translocations. Comparative genomic hybridization (CGH) revealed numerous regions of copy number aberration (CNA). Further analysis by array CGH identified 27 regions of CNA (16 amplified, 11 deleted). Thirty-eight percent of the genes in the amplified regions were overexpressed, compared to only 9% in regions of normal copy number ratios (CNR). Accordingly, 26% of the genes in the deleted regions were underexpressed, compared to 10% in regions of normal CNR. Most amplified and overexpressed genes were located on chromosome 1 as well as on 8q, 12q14.1, 17q11 approximately q21, and 20q13. In 17q11 approximately q21, we identified two separate amplicons, the HER-2 amplicon and a previously unreported amplicon at 17q21.31. Several aberrant genes are implicated in cancer development (e.g., JUN, CDK4, and SLUG protooncogenes, as well as the drug/hormone-metabolizing genes GSTM1 and CYP24). We conclude that cytogenetic and expression profiling of JIMT-1 revealed several new features that need further characterization and may shed light on trastuzumab resistance.     

Molecular cytogenetic evaluation of 10 uveal melanoma cell lines

Uveal melanoma is the most common intraocular tumor in adults and often results in unilateral blindness and/or death. Previous cytogenetic characterizations of this tumor consistently revealed chromosomal abnormalities involving chromosomes 3, 6, and 8; reports of other abnormalities vary in frequency. We defined cytogenetic abnormalities of this tumor using complementary in situ hybridization techniques on 10 uveal melanoma cell lines. Synthesis of comparative genomic hybridization (CGH) and spectral karyotyping (SKY) results revealed that chromosomal rearrangement is involved in DNA sequence copy number abnormalities throughout the genome, but monosomy 3 was not found. Monosomy 3 is thought to be a significant prognostic indicator, so its absence was investigated further. Fluorescence in situ hybridization (FISH) for chromosome 3 revealed approximately 1 centromere signal per cell, but probes for 3p and 3q revealed multiple telomere signals per cell, suggesting chromosomal rearrangement without whole-chromosome loss. Based on combined CGH, SKY, and FISH data, we propose that chromosome 3 is more frequently involved in chromosomal rearrangements than whole-chromosome loss in uveal melanoma. Future approaches should be designed to confirm and enhance the resolution of regions of imbalance in primary tumors. Once identified, conserved chromosomal alterations that contribute to uveal melanoma may reveal the underlying aspects of uveal melanoma onset, metastasis and resistance to current treatment modalities.     

Origin of histiocyte-like cells and multinucleated giant cells in malignant fibrous histiocytoma: Neoplastic or reactive?

The origin of histiocyte-like cells in malignant fibrous histiocytoma (MFH) remains controversial. To determine whether histiocyte-like cells and multinucleated giant cells show reactive or neoplastic proliferation, we transplanted human storiform-pleomorphic MFH to nude mice and investigated the origin of histiocyte-like cells using the DNA in situ hybridization (ISH) system. In addition, we analyzed the mRNA expression of mouse c-fms and human colony stimulating factor-1 (CSF-1); immunohistochemical expression of markers detectable in cells of monocyte/macrophage lineage. The DNA ISH revealed neoplastic proliferation of fibroblastic cells and bizarre multinucleated giant cells of human origin. Monocyte/macrophage lineage cells were seen in parental tumors, whereas they did not participate in neoplastic proliferation in transplanted tumors. The parental tumors expressed human CSF-1 mRNA and the histiocyte-like cells in transplanted tumors expressed 'mouse' c-fms mRNA. These results suggest that MFH induce infiltration of monocyte/macrophage and CSF-1 is one of the mediators involved in this phenomenon, because the human CSF-1 can act as a ligand to the mouse c-fms. Histiocyte-like cells in MFH should be considered as a reactive monocyte/macrophage lineage rather than as an element of neoplasm.     

DNA copy number changes detected by comparative genomic hybridization and their association with clinicopathologic parameters in breast tumors

The purpose of this study was to use comparative genomic hybridization (CGH) to screen breast tumors for copy number changes: 22 ductal, 9 lobular, 7 mixed, 2 micropapillary carcinomas, and 2 ductal carcinoma in situ were studied and various regional genomic imbalances were detected. The majority of the aberrations identified in this study were in line with previous CGH findings. The most frequent DNA sequence copy number changes were 1q, 8q, and 20q gains. The frequency of 16q losses was significantly higher in lobular carcinomas. The nodal involvement was 10 times higher in cases showing losses of 13q than in cases having normal peak profile at this region. Estrogen receptor positivity was significantly higher in cases displaying 20q gains and 16q losses. Unambiguous high-level DNA amplifications have also been detected. These mapped to 4q31, 6q21 approximately q22, 8q21 approximately q24, 8p11.2 approximately p12, 11q13, 15q24 approximately qter, 20q13.1 approximately qter, and 20q12 approximately qter chromosomal locations. Our results highlight several chromosomal regions that may be important in the molecular genetics of distinct clinicopathologic breast cancer subgroups.     

Carcinoma of the parotid gland with osteoclastlike giant cells. Immunohistochemical and ultrastructural observations

We describe an unusual type of carcinoma of the parotid gland in a 67-year-old man. Because of rapid tumor growth, radical parotidectomy was done. Light microscopic study of the tumor revealed focal gland formation with transition to anaplastic carcinoma. Among the undifferentiated mononuclear cells and bizarre large cells were scattered many osteoclastlike multinucleated giant cells. Immunohistochemical studies on paraffin sections revealed positive staining for epithelial membrane antigen in the epithelial component; however, the multinucleated giant cells were clearly negative for this antigen. Reactions for other cell constituents (carcinoembryonic antigen, alpha 1-antitrypsin, alpha-1-antichymotrypsin, Leu-M1, Leu-M3, lysozyme, and factor VIII-related antigen) were negative in both epithelial and giant cell components of the tumor. Electron microscopy revealed poorly formed cell junctions and numerous microvilli on the surface of the mononuclear tumor cells and multinucleated giant cells, features considered not of diagnostic significance. Similar to carcinomas with osteoclastlike multinucleated giant cells in other organs, this parotid gland tumor has shown clinical and morphologic evidence of aggressive growth; pulmonary metastases developed and the patient died 28 months after radical surgery.     

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.     

Genomic alterations in lung adenocarcinomas detected by multicolor fluorescence in situ hybridization and comparative genomic hybridization

We used two molecular cytogenetic techniques, multicolor fluorescence in situ hybridization (M-FISH) and comparative genomic hybridization (CGH), to analyze three established lung adenocarcinoma cell lines (A549, H1650, and SPC-A-1) and primary lung adenocarcinoma samples, to identify common chromosomal aberrations. M-FISH revealed numerous complex chromosomal rearrangements. Chromosomes 5, 6, 11, 12, and 17 were most frequently involved in interchromosomal translocations. CGH revealed regions on 1q, 2p, 3q, 5p, 5q, 7p, 8q, 11q, 12q, 14q, 16p, 17p, 19q, 20q, 21q, and 22q to be commonly overrepresented and regions on 2q, 3p, 4p, 5q, 7q, 8p, 9p, 13q, 14q, and 17p to be underrepresented. The most common gains were found in 16p13 (in 50% of samples), and 16p13 amplification was associated with relatively poor differentiation and late stage. M-FISH and CGH can be a powerful tool in identification of genomic alterations in lung cancer, as well as in diagnosis. The overrepresented regions may harbor potential candidate genes involved in lung adenocarcinoma pathogenesis.     

Comparative genomic hybridization analysis identifies gains of 1p35 approximately p36 and chromosome 19 in osteosarcoma.

Osteosarcomas (OS) are aggressive tumors of the bone and often have a poor prognosis. Conventional cytogenetic analyses of OS have revealed highly complex karyotypes, with numerous abnormalities. In this study, we analyzed 18 untreated OS tumors from 17 patients of the younger incidence age group by comparative genomic hybridization (CGH), 4 tumors by spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH). Comparative genomic hybridization identified frequent copy number changes of the chromosomal region 1p (10/17) and gain of part or all of chromosome 19(8/17). In addition gains were observed at 5p(3/17), 8q(3/17), 16p(3/17), and 17p(5/17); and losses at chromosomes 2q(3/17), 10(4/17) and 13(3/17). High level gains were detected in the 8q23 approximately q24 region in two tumors as well as at 17p in one primary and a metastatic tumor. Minimal regions of gain were present at 1p35 approximately p36.3 (8/17); 5p14 approximately p15.2 (3/17), and 8q22 approximately q24.3 (3/17). SKY analysis demonstrated that OS has a complex pattern of clonal and non-clonal rearrangements and helped confirm the structural basis for the imbalances detected by CGH. Spectral karyotyping confirmed an overall pattern of chromosomal gain affecting 1p in all four tumors. Fluorescence in situ hybridization analysis from these tumors confirmed the gain of the 1p36 region in 2 tumors as determined by CGH analysis as well as the amplification of 8q.     

解整合素-金属蛋白酶1 2基因在骨巨细胞瘤组织中的表达及意义

目的 检测解整合素-金属蛋白酶12（ADAM12）基因在骨巨细胞瘤组织中的表达和定位,探讨其对骨巨细胞瘤中多核巨细胞形成的作用。方法 用逆转录-聚合酶链反应（RT-PCR）检测18例、用RNA原位杂交检测12例骨巨细胞瘤患者的瘤组织、6倍体外培养骨巨细胞瘤瘤细胞、2例胚胎横纹肌和5例成人横纹肌组织的ADAM12mRNA。结果 RT-PCR显示,18例骨巨细胞瘤组织中,12例（67%）有ADAM12mRNA表达;RNA原位杂交则显示12例骨巨细胞瘤组织全部呈ADAM12阳性反应,并且位于几乎所有的多核巨细胞和单核基质细胞质中。随着骨巨细胞瘤培养细胞传代次数的增多和多核巨细胞的消失,ADAM12mRNA的表达也逐渐消失。结论 骨巨细胞瘤中的多核巨细胞可能是由单核基质细胞融合而成,ADAM12基因参与这一融合过程。     

Establishment of a new human malignant fibrous histiocytoma cell line,FU-MFH-1: cytogenetic characterization by comparative genomic hybridization and fluorescence in situ hybridization

Although a number of malignant fibrous histiocytoma (MFH) cell lines have been reported, their characterization at a molecular cytogenetic level has not been fully established. In this study, we established a new human cell line, designated as FU-MFH-1, from a storiform-pleomorphic MFH arising in the retroperitoneum of a 61-year-old woman, and applied comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH) with chromosome painting probes for the characterization of chromosome alterations. FU-MFH-1 cells were spindle, round, or polygonal in shape with oval nuclei, and were maintained continuously in vitro for over 50 passages for more than 12 months. G-banding analysis was performed and FU-MFH-1 revealed a complex karyotype with an abnormal chromosome 19 containing a homogeneously staining region (hsr). CGH analysis showed a high-level amplification of 12q13-->q21. The high-level amplification detected by CGH was refined by FISH. These results showed that the hsr was composed of amplified DNA sequences from 12q. Our study emphasizes the usefulness of CGH as a powerful tool for chromosomal localization of amplified sequences. The FU-MFH-1 cell line should be useful for biologic and molecular pathogenetic investigations of human MFH.     

Common genomic aberrations in basaloid squamous cell carcinoma and carcinosarcoma of the esophagus detected by CGH and array CGH

Basaloid squamous cell carcinoma (BSCC) and carcinosarcoma of the esophagus are rare entities, making up fewer than 2% of esophageal malignancies. Comparative genomic hybridization (CGH) in 1 case of BSCC and 2 cases of carcinosarcoma and subsequent array CGH in 1 case each of BSCC and carcinosarcoma revealed common chromosomal gains at 2p25.3-2p12, 7q21.3-7q22.3, and 11q13.2-11q13.4. Chromosomal losses at 13q31qter were observed in both carcinosarcomas. In addition, progression of genomic instability from in situ to invasive carcinosarcoma could be demonstrated by using array CGH. Our observations suggest a common genetic origin of BSCC and carcinosarcoma.     

Molecular cytogenetic abnormalities in multiple myeloma and plasma cell leukemia measured using comparative genomic hybridization

Comparative genomic hybridization (CGH) was used to identify recurrent regions of DNA sequence loss and gain in 21 multiple myeloma (MM) and plasma cell leukemia (PCL) primary tumor specimens and cell lines. Multiple regions of non-random sequence loss and gain were observed in 8/8 primary advanced stage tumors and 13/13 cell lines. Identification of sequence copy number changes was facilitated by statistical analyses that reduce subjectivity associated with identification of copy number changes and by requiring that sequence changes are visible using both red- and green-labeled tumor DNA. Loss of sequence on 13q and 14q and gain of sequence on 1q and chromosome 7 occurred in 50–60% of the population. In general, cell lines carry more and larger regions of sequence gain and loss than primary tumors. Regions of sequence copy number change that recur among MM cell lines and primary tumors include, in order of prevalence, enh(1q12qter), dim(13), enh(7), enh(3q22q29), enh(11q13.3qter), dim(14q11.2q31), enh(8q21qter), enh(3p25pter), dim(17p11.2p13), and dim(6q22.1q23). Population distributions of genome-wide changes in primary tumors reveal “hot-spots” of sequence loss from 13q12.1-q21, 13q32-q34, 14q11.2-q13, and 14q23-q31. Genomic changes detected using CGH are consistent with those identified using banding analyses, although recurrent involvement of additional regions of the genome are also evident. A higher prevalence of genomic changes is visible using CGH compared to banding. Identification of recurrent regions of sequence gain and loss provides opportunities to identify regions of the genome that may be involved in the malignant phenotype and/or disease progression. Genes Chromosom. Cancer 19:124–133, 1997. © 1997 Wiley-Liss, Inc.     

Screening for submicroscopic chromosomal rearrangements in Wilms tumor using whole-genome microarrays

Wilms tumor is the fourth most common malignancy of childhood; its pathogenesis, however, remains largely unknown. With advancements in cytogenetic techniques, such as array comparative genomic hybridization (aCGH), there is new hope for uncovering small chromosomal microdeletions or microduplications that may contribute to our understanding of Wilms tumor. We performed aCGH on 10 samples of Wilms tumor with normal conventional cytogenetic and chromosomal CGH findings. Array CGH revealed abnormalities in 3 of the 10 samples, including microdeletions (2q37.1, 7q31 approximately q32, and 11q22.3), microduplication (18q21.1), and gains and losses of larger chromosomal areas (1q and 7q gain and loss of 7p, 11q, 14q, and 16q). Fluorescence in situ hybridization (FISH) analysis confirmed the abnormalities and revealed the majority of them existed only in a proportion cells (> or =30% of cells). We also performed aCGH on three samples of Wilms tumor with previously identified translocations between chromosomes 1 and 16, to determine the breakpoints. The breakpoints were seen in the pericentromeric regions of both chromosomes. Array CGH is useful for identifying submicroscopic changes in Wilms tumor and is more sensitive for detecting clonal abnormalities than conventional methods.     

Complete cytogenetic characterization of the human breast cancer cell line MA11 combining G-banding, comparative genomic hybridization, multicolor fluorescence in situ hybridization, RxFISH, and chromosome-specific painting.

The MA11 cell line was established from malignant cells isolated from the bone marrow of a breast cancer patient. It metastasizes selectively to the brain in athymic mice. Since the genomic rearrangements of only a few breast cancer cell lines have been characterized completely, we analyzed MA11 cytogenetically. Because the G-banding analysis revealed a very complex karyotype with several markers and chromosomes with additional material of unknown origin, we used multicolor fluorescence in situ hybridization (M-FISH), cross-species color banding (RxFISH), comparative genomic hybridization (CGH), and chromosome-specific probes to better characterize the chromosome abnormalities. The use of these FISH-based screening techniques allowed us to detect previously unsuspected chromosomal changes and determine the identity of chromosomal markers. Multicolor FISH was especially useful to identify the rearranged chromosomes, whereas RxFISH, G-banding, and CGH were instrumental in determining breakpoint positions, although some uncertainties were removed only after hybridization with chromosome-specific probes. The combined analysis revealed a near-triploid karyotype with no less than 20 chromosomes demonstrating structural rearrangements. The resulting imbalances included several of those known to be common in primary breast carcinomas (gain of 1q, 8q, and 20q and loss of 8p, 11q, and 13q), indicating that the MA11 cell line may serve as a good model to study breast carcinogenesis. The full cytogenetic characterization we present may guide future searches for the mechanism of organ-selective metastasis in this model system and, possibly, also in vivo.     

Genetic changes in localized prostate cancer of Japanese patients shown by comparative genomic hybridization

To search for additional amplification and deletion sites that may serve as a starting point for the discovery of new oncogenes or tumor suppressor genes, 30 Japanese localized prostate cancers were analyzed by comparative genomic hybridization (CGH) in this study. CGH was used to search for changes in DNA sequence copy-number in a series of 30 primary prostate adenocarcinomas, consisting of 22 cases of pT2N0 (organ confined; without capsular invasion) and 8 cases of pT3N0 (with capsular invasion), removed by radical prostatectomy. CGH revealed that the shortest regions of overlap (SRO) of gains in pT2N0 were at 8q22.2 approximately q24.2, 11q13.1 approximately q14.1, and 12q23 approximately q24.2, whereas the SRO of losses were seen at 8p23.3 approximately p22, 13q21.2 approximately p22, and 18q21 approximately q22. The SRO of gains in pT3N0 were noted at 5q32 approximately q34, 8q22.3 approximately q24.1, 11q14.1 approximately q22.3, and 12q22 approximately q24.2, whereas the SRO of losses were seen at 18q21.2 approximately q23. These results suggest that gains or losses of DNA in these regions are important for prostate cancer progression. The detection of the SRO may serve as a starting point to discover novel oncogenes and tumor suppressor genes involved in prostate cancer progression.     

Characterization of large chromosome markers in a malignant fibrous histiocytoma by spectral karyotyping, comparative genomic hybridization (CGH), and array CGH

In this study, we characterized the chromosomal composition of an intra-abdominal soft tissue sarcoma diagnosed as a malignant fibrous histiocytoma (MFH). By applying a combination of spectral karyotyping, G-banding, and comparative genomic hybridization (CGH), this case was shown to carry large chromosome markers with material mainly from chromosomes 6 and 8. Further characterization of this unique tumor revealed high-level amplifications at the 6q21 approximately q23, 8p21 approximately pter, 8q24 approximately qter, and 12q13 approximately q21 regions. Using array CGH, these amplified regions were found to include MASL1 in 8p, as well s MDM2 and CDK4 in 12q, which have been shown to be amplified in MFH. Similarly, gains of 6q and 8q have also been seen in MFH. In conclusion, our study demonstrates the occurrence of large chromosome markers in MFH and suggests that the regions 6q21 approximately q23, 8p21 approximately pter, 8q24 approximately qter, and 12q13 approximately q21 might harbor oncogenes that could play a role in MFH's tumorigenesis. In addition, gain of 12q13 approximately q21, which is typical of well-differentiated liposarcoma, may also occur in MFH, supporting the previously suggested overlap in genetic etiologies between these two tumor types.     

High-resolution analysis of allelic imbalance in neuroblastoma cell lines by single nucleotide polymorphism arrays

Genomic copy number changes are detectable in many malignancies, including neuroblastoma, using techniques such as comparative genomic hybridization (CGH), microsatellite analysis, conventional karyotyping, and fluorescence in situ hybridization (FISH). We report the use of 10K single nucleotide polymorphism (SNP) microarrays to detect copy number changes and allelic imbalance in six neuroblastoma cell lines (IMR32, SHEP, NBL-S, SJNB-1, LS, and SKNBE2c). SNP data were generated using the GeneChip DNA Analysis and GeneChip chromosome copy number software (Affymetrix). SNP arrays confirmed the presence of all previously reported cytogenetic abnormalities in the cell lines, including chromosome 1p deletion, MYCN amplification, gain of 17q and 11q, and 14q deletions. In addition, the SNP arrays revealed several chromosome gains and losses not detected by CGH or karyotyping; these included gain of 8q21.1 approximately 24.3 and gain of chromosome 12 in IMR-32 cells; loss at 4p15.3 approximately 16.1 and loss at 16p12.3 approximately 13.2, 11q loss with loss of heterozygosity (LOH) at 11q14.3 approximately 23.3 in SJNB-1 cells; and loss at 8p21.2 approximately 23.3 and 9p21.3 approximately 22.1 with corresponding LOH in SHEP cells. The SNP arrays refined the mapping of the 2p amplicons in LS, BE2c, and IMR-32 cell lines, the 12q amplicon in LS cells, and also identified an 11q13 amplicon in LS cells. There was good concordance among SNP arrays, CGH, and karyotyping. SNP array analysis is a powerful tool for the detection of allelic imbalance in neuroblastoma and also allows identification of LOH without changes in copy number (uniparental disomy).     

Conventional and array-based comparative genomic hybridization analysis of nasopharyngeal carcinomas from the Mediterranean area

Nasopharyngeal carcinoma (NPC) occurs with a high incidence in Southeast Asia and to a lesser extent in the Mediterranean area, especially in Tunisia, Algeria, and Morocco. Cellular gene alterations combined with latent Epstein-Barr virus infection are thought to be essential for NPC oncogenesis. To date, chromosome analysis with comparative genomic hybridization (CGH) has been reported exclusively for NPCs from Southeast Asia. Although NPCs from the Mediterranean area have several distinct clinical and epidemiological features, CGH investigations have been lacking. Chromosome analysis was therefore undertaken on a series of NPC xenografts and biopsies derived from patients of Mediterranean origin. Four xenografts were investigated with a combination of conventional CGH, array-based CGH, and comparative expressed sequence hybridization. In addition, 23 fresh NPC biopsies were analyzed with conventional CGH. Data obtained from xenografts and fresh biopsies were consistent, except that amplification of genes at 18p was observed only in xenografts derived from metastatic tissues. Frequent gains associated with gene overexpression were detected at 1q25 approximately qter (64%) and 12p13 (50%). Losses were noticed mainly at 11q14 approximately q23 (50%), 13q12 approximately q31 (50%), 14q24 approximately q31 (43%), and 3p13 approximately p23 (43%). Comparison with previous reports suggests that Mediterranean NPCs have higher frequencies of gains at 1q and losses at 13q than their Asian counterparts.