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.     

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.     

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.     

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.     

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.     

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.     

Characterization of cyanobacteria by SDS-PAGE of whole-cell proteins and PCR/RFLP of the 16S rRNA gene

Childhood neuroblastoma, an embryonal neoplasm of sympathetic nervous system progenitors, occurs in a familial form with an autosomal dominant mode of inheritance. Genetic susceptibility to this disorder is thought to arise via a germline mutation affecting a tumor suppressor gene, in accord with the two-hit model established for familial and sporadic retinoblastoma. Surprisingly, the familial neuroblastoma predisposition locus does not map to chromosome band 1p36, a genomic region likely to contain one or more neuroblastoma suppressor genes. We reasoned that inherited point mutations affecting one allele would be unmasked in many cases by somatically acquired deletions of the second allele that included the target gene in the tumor cells from these patients. Thus, to identify chromosomal regions that might contain suppressor genes important in hereditary neuroblastoma, we analyzed six familial tumors by comparative genomic hybridization. Recurrent losses of genetic material were detected on chromosome arms 3p (consensus region, 3p24-pter), 10p (consensus, 10p12-p13), 10q (consensus, 10q25-qter), 16q (consensus, 16q12-q22), and 20q (consensus, 20q13.3-qter), in addition to the regions commonly deleted in sporadic neuroblastomas (1p36 and 11q). These chromosomal sites may harbor novel tumor suppressor genes that could aid in our understanding of the predisposition to and pathogenesis of familial neuroblastoma and potentially sporadic tumors as well.     

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.     

Identification of a novel gene, MASL1, within an amplicon at 8p23.1 detected in malignant fibrous histiocytomas by comparative genomic hybridization

We used comparative genomic hybridization to study malignant fibrous histiocytomas (MFHs) from 19 patients to detect changes in the copy number of DNA sequences, along entire chromosomes. Together with losses and gains in various chromosomal regions, distinct high-level amplifications were found at six loci (4q12-21, 8p21-pter, 8q24.1-qter, 9q12-13, 12p11.2-pter, and 15q11.2-15), suggesting that those regions may contain unknown (proto) oncogenes. We focused on the 8p amplicon, where detailed characterization allowed us to determine that the minimal common amplified region lay between markers D8S1819 and D8S550 at 8p23.1. A novel gene designated MASL1 (MFH-amplified sequences with leucine-rich tandem repeats 1) was isolated from within this narrowly defined region. Expression of the MASL1 gene was enhanced significantly in MFH tumors bearing the 8p amplicon. The primary structure of its deduced product revealed an ATP/GTP-binding site, three leucine zipper domains, and a leucine-rich tandem repeat, all of which are important structural or functional elements for interactions among proteins related to the cell cycle. These features suggest that overexpression of MASL1 might well be oncogenic with respect to MFH.     

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.     

Cyclin D1/PRAD1 as a central target in oncogenesis

Understanding the genetic elements controlling the process of tumor metastasis to distant organ sites such as the liver may be the key to improving survivorship from colon cancer. By using standard cytogenetic techniques in combination with comparative genomic hybridization, multiple genetic imbalances within three human colon cancer cell lines previously selected for differences in liver-metastatic behavior were identified. The entire genome of one poorly metastatic cell line (KM12C) was compared directly with that of two highly metastatic cell lines (KM12SM, KM12L4A) derived from it. A number of chromosomal gains (8q, 12q15, 20q11.2) and losses (5p13, 6p21.3, 18) were common to all three cell lines and are likely related to early tumor development rather than to the selection process used to generate cell lines of increased metastatic potential. Chromosomal imbalances detected only in the highly metastatic cell lines were also observed. KM12SM showed losses of portions of 2p22, 2q24.3--> 2q32.2, 4p15.3--> cen, 4q24 without the 13q and 15q22.3 gains noted for KM12C. Both gains (1p31.3--> 1p21, 2q22--> 2q33, 3cen--> 3q26.2, 5q14--> 5q23, 6cen--> 6q23) and losses (16p, 17p, 17q 19p, 19q 22q) were observed for KM12L4A but not for the other two cell lines. Identification of these alterations provides valuable insight into the process of experimental liver metastasis and is a first step towards mapping genes linked to the terminal phases of human colon cancer progression.     

Daxx, a novel Fas-binding protein that activates JNK and apoptosis

We examined 33 primary gastric carcinomas using comparative genomic hybridization to detect changes in the DNA copy number and the chromosomal location of these changes. Ninety-four percent (31 of 33) showed 1 or more DNA copy number changes, such as increases at 2p23-p25 (observed in 21% of the total cases), 3q26.3-q27 (24%), 7p15 (24%), 9p22-pter (18%), and 13q22-q34 (21%) and decreases at 1p34.2-p36.2 (18%) and Y (52%). Histological examination indicated that increases at 3q26.1-q26.3 and 7p15 and decreases at 1p36.1-p36. 2 and Y were commonly observed in both differentiated and undifferentiated types. Increases at 3q27, 6q23-q25, and 7cen-p14 and decreases at 1p34.2-p35 and 17p12 were predominantly observed in the differentiated type, and increases at 2p23-pter, 9p22-pter, and 13q31-qter and a decrease at 6p21.3 were predominantly observed in the undifferentiated type. In addition, clinical staging of tumors showed that increases at 2p23-p25, 7p14-p21, 7q31-q32, and 9p22-pter and a decrease at Y were observed in early-stage tumors, whereas increases at 9q32-q33 and 15q26 were observed only in late-stage tumors. Many of the abnormalities detected in this study were not previously reported in gastric carcinomas. Our comparative genomic hybridization results indicate the presence of genetic alterations that may play some important role in the development and progression of gastric carcinomas.     

Comparative genomic hybridization and its application to Wilms' tumorigenesis

Eighty sporadic Wilms' tumor samples were analyzed by comparative genomic hybridization (CGH) to identify chromosomal regions involved in the etiology of the disease. Twenty percent of the samples showed chromosomal gains or losses. The majority of chromosomal gains and losses were similar to those identified through molecular and cytogenetic studies. Gains were observed on chromosomes 1q, 7q, 8, and 12, whereas losses were found on chromosomes 1p, 4p, 4q, 7p, 16q, 18q, 21q, and 22q. Other genetic aberrations identified in this study included deletions of chromosomes 5p and 15q, as well as gains of discrete loci on chromosomes 3p and 3q. These latter regions have not been previously implicated in Wilms' tumorigenesis and may contain novel genes relevant to the development and/or progression of this disease.     

Chromosomal abnormalities in glioblastoma multiforme tumors and glioma cell lines detected by comparative genomic hybridization

Comparative genomic hybridization (CGH) is a recent molecular cytogenetic method that detects and localizes gains or losses in DNA copy number across the entire tumor genome. We used CGH to examine 9 glioma cell lines and 20 primary and 10 recurrent glioblastoma tumors. More than 25% of the primary tumors had gains on chromosome 7; they also had frequent losses on 9p, 10, 13 and Y. The losses on chromosome 13 included several interstitial deletions, with a common area of loss of 13q21. The recurrent tumors not only had gains on chromosome 7 and losses on 9p, 10, 13 and Y but also frequent losses on 6 and 14. One recurrent tumor had a deletion of 10q22-26. Cell lines showed gains of 5p, 7 and Xp; frequent amplifications at 8q22-24.2, 7q21-32 and 3q26.2-29 and frequent losses on 4, 10, 13, 14 and Y. Because primary and recurrent tumors and cell lines showed abnormalities of DNA copy number on chromosomes 7, 10, 13 and Y, these regions may play a fundamental role in tumor initiation and/or progression. The propensity for losses on chromosomes 6 and 14 to occur in recurrent tumors suggests that these aberrations play a role in tumor recurrence, the development of resistance to therapy or both. Analysis of common areas of loss and gain in these tumors and cell lines provides a basis for future attempts to more finely map these genetic changes.     

Cytogenetic and fluorescence in situ hybridization characterization of chromosome 1 rearrangements in head and neck carcinomas delineate a target region for deletions within 1p11-1p13

Cytogenetic analyses have revealed structural rearrangements of chromosome 1 in a large fraction of head and neck carcinomas (HNCA). These aberrations frequently affect chromosomal band 1p13 and the centromeric region, the latter often in the form of isochromosome i(1q) and whole-arm translocations. To delineate the critical region involved in rearrangements of proximal 1p, we have undertaken a more precise breakpoint mapping in 13 HNCAs, using metaphase fluorescence in situ hybridization with 11 yeast artificial chromosome (YAC) clones spanning 1p. All of the tumors had chromosome 1 changes at G-banding analyses. Fluorescence in situ hybridization showed that in almost all of the cases, at least one copy of chromosome 1 was affected by centromeric rearrangement. By the use of YAC clones mapped to juxtacentromeric regions and a centromere-specific alpha-satellite probe, we detected variable breakpoints in the whole-arm translocations. At the cytogenetic level, 1p13 rearrangements were frequent. However, molecular breakpoints within this band varied among the HNCAs tested. The lack of consistently rearranged chromosome segments indicates that the pathogenetically important consequence of 1p rearrangements in HNCAs is loss and/or gain of genes outside the breakpoint regions. In an assessment of the genomic imbalances, partial or complete overrepresentation of 1q was seen in eight cases. Loss of 1p material was also identified in eight cases; and in four of them, the deleted segments were too small to be discovered by G-banding analysis. The minimal overlapping deleted region was in the interval between YAC 959C4 (band p11-p12) and the centromere (p10). Our findings indicate that a target region potentially harboring tumor suppressor gene(s) crucial for HNCA is located within chromosomal bands 1p11-p13.     

A peripheral hospital can be fulfilling--for staff and patients alike

Comparative genomic hybridization (CGH) is a powerful new technique for the molecular cytogenetic analysis of cancer. In this method, at first the cancer DNA and normal DNA are labeled with biotin and digoxigenin, respectively, and then the labeled DNAs are applied onto normal lymphocyte metaphase preparations in hybridization. After hybridization, they are stained with FITC and rhodamine, respectively, so chromosomal gains and losses in cancer are thus detected by using a green:red ratio. In this study, we analyzed the abnormal chromosomes in nine cases with human primary colon cancer. A gain in chromosomes 11p, 12q, 16p, 20p, and 20q were observed, while a loss of 18q and 22q were discovered. CGH may thus provide us with important information for analyzing the genes in colon cancer.     

Distinct patterns of chromosomal alterations in high- and low-grade head and neck squamous cell carcinomas

Comparative genomic hybridization was performed on 30 primary head and neck squamous cell carcinomas. Fractional or entire DNA loss of chromosome 3p was a basic finding that occurred in 29 cases (97%). Additional DNA underrepresentations were observed in more than 50% of the cases on chromosomes 1p, 4, 5q, 6q, 8p, 9p, 11q, 13q, 18q, and 21q. Deletions on chromosomes 3p, 13q, and 17p were confirmed by loss of heterozygosity analysis. Entire or partial DNA copy number increases were identified for chromosome 3q in 26 cases (87%) with high-level amplifications at 3q24 and 3q27-qter. Overrepresentations were found in decreasing order of frequency at 11q13 (70%), 8q (57%), 19q (50%), 19p (47%), and 17q (47%). The use of comparative genomic hybridization superkaryograms of the group of well-differentiated carcinomas (G1) indicated that the deletions on chromosomes 3p and 9p along with the overrepresentation of 3q are associated with early tumor development. Accordingly, the undifferentiated tumors (G3) were characterized by additional deletions on chromosomes 4q, 8p, 11q, 13q, 18q, and 21q and overrepresentations on 1pter, 11q13, 19, and 22q, suggesting that these changes are preferentially associated with tumor progression.     

Hematologic malignancies with t(4;11)(q21;q23)--a cytogenetic, morphologic, immunophenotypic and clinical study of 183 cases. European 11q23 Workshop participants

A total of 183 hematologic malignancies with t(4;11)(q21;q23), including five variant translocations, were collected by the Workshop. Clinical, morphologic and immunophenotypic features were compiled, and karyotypes with variant t(4;11) or secondary chromosomal aberrations were reviewed. All cases were acute leukemias (AL): 173 acute lymphoblastic leukemias (ALL), six acute myeloid leukemias (AML), three unclassifiable AL, and one biphenotypic AL. Ten patients had treatment-associated AL. Females were overrepresented (104 vs 79) and the age distribution was clearly nonrandom; 34% of the cases occurred in infants below the age of 12 months. The remaining AL were evenly distributed among the other age groups, with the oldest patient being 79 years old. An increased white blood cell count (WBC) was reported in more than 90% of the cases, with hyperleukocytosis (> or =100 x 10(9)/l) in 64%. Additional chromosomal changes were detected in 55 (30%) cases, most often gain of the X chromosome, i(7)(q10), and trisomy 8, with frequent breakpoints in 1p36, 1q21, 7q10, 11p15, 12p13, 17p11, and 17p10. All recurrent secondary changes resulted in genomic imbalances, in particular gains of 1q, 7q, 8, and X and losses of 7p and 17p. Event-free and overall survival (EFS and OS) could be ascertained in 170 and 171 patients, respectively. Kaplan-Meier estimates of EFS and OS showed no differences with regard to gender, WBC, or presence of secondary chromosomal abnormalities, and there was no increase of EFS or OS among the 55 cases that had undergone bone marrow transplantation. However, age had an important prognostic impact, with significantly (P < 0.0001) longer EFS and OS in children 2-9 years old than among infants and younger children, patients aged between 10 and 39 years and older adults.     

Detection of chromosomal aberrations in seminomatous germ cell tumours using comparative genomic hybridization

Comparative genomic hybridization (CGH) was used to evaluate tissue specimens from 16 seminomas in order to elucidate the pathogenesis of germ cell tumours in males. A characteristic pattern of losses and gains within the entire genomes was detected in 94% of the seminomas by comparing the ratio profiles of the tumours with a standard of cytogenetically normal genomic DNA. Losses represented 43% of the total number of alterations often affecting chromosomes and chromosome arms 4, 5, 11, 13q, and 18q. Gains amounted to 57% and were often observed on 1q, 7, 8, 12, 14q, 15q, 21q, and 22q. Aberrations of 12p and 21q appeared most consistently. Results from CGH analysis displayed no relationship to the clinical stages of the malignancy. Some rare aberrations appeared, however, only in clinical stage II and in tumours showing relapse in the contralateral testis following orchiectomy, although the alterations were not present in all of the tumours in question. Losses of 16q13-21 and gains of 9q22.1-22.2 were demonstrated in both groups, while loss of 16p12 and gains of 6p21 and 6q23.3-24 were detected in the latter group as well. In conclusion, a specific pattern of chromosomal alterations was demonstrated in the seminomas by improved detection criteria, which increased specificity and sensitivity. The rare aberrations, which appeared only in tumours in improved detection criteria, which increased specificity and sensitivity. The rare aberrations, which appeared only in tumours in clinical stage II and relapsed tumours, may be linked to tumour progression, invasiveness, and bilateral disease.     

Canada''s healthcare system: what now, eh?

Using comparative genomic hybridization (CGH), we have identified and mapped regions of DNA amplification in primary and metastatic osteosarcomas. Samples were obtained from four patients and ten independent xenografts. Sixty-four percent of the tumors showed increased DNA-sequence copy numbers, affecting 23 different chromosomal sites. Most of these regions were not previously associated with the development and/or progression of these tumors. Amplicons originating from 1q21-q23, 6p, 8q23-qter, and 17p11-p12 were observed most frequently. The 6p and 17p11-p12 amplicons seem to be specific for osteosarcomas, indicating that these regions may harbor genes relevant for the development of these tumors.