Biomedical subjects

C Brinkschmidt

Publications and source records attributed to C Brinkschmidt.

31 records · Page 2Linked to original sources

PubMed1999

Sublocalization of putative tumor suppressor gene loci on chromosome arm 14q in neuroblastoma.

RFLP and microsatellite analysis with 23 polymorphic markers spanning the entire long arm of chromosome 14 in 108 neuroblastomas showed allelic loss in 19 out of 107 (18%) informative tumors, placing 14q among the most frequently affected chromosomal regions in neuroblastoma. One minimal deletion region could be sublocalized in 17 of 19 cases between markers D14S1 and D14S16, and a second one between markers D14S17 and D14S23 in band 14q32. Furthermore, breakpoints in bands 14q23 and 14q12 were detected. These results suggest the presence of at least two putative tumor suppressor gene loci on chromosome 14. Survival analyses revealed no prognostic impact of allelic loss of 14q in neuroblastoma. Genes Chromosomes Cancer 26:40-46, 1999.

Chromosome Mapping↗

PubMed1998

Chromosomal aberrations associated with invasion in papillary superficial bladder cancer.

Non-invasive and invasive papillary transitional cell carcinomas of stages pTa and pT1 represent the first steps of tumour progression in bladder cancer. In order to analyse different chromosomal alterations of pTa and pT1 superficial bladder cancer, 46 tumour specimens were examined by comparative genomic hybridization (CGH). Losses of chromosome 9 material (11/20) and gains of chromosome 17 material (6/20) were frequently found in pTa tumours. Stage pT1 tumours were characterized by gains of chromosome 1q (14/26; including amplification at 1q21-q24 in three cases) and chromosome 17 material (15/26), as well as by losses of 11p (15/26) and 11q (13/26). Other loci frequently showing losses in pT1 tumours were 2q (9/26), 4q (10/26), 5q (9/26), 8p (10/26), 9p (9/26), 9q (12/26), 10q (8/26), 17p (7/26), and 18q (8/26). Amplifications were detected at 8q21/22, 5q21, 7q36, 10p14, 10p12, 10q25, 12q12, and 12q14. The most striking differences between grade 2 pTa and pT1 tumours were gains of 1q (P < 0.01) and losses at 2q (P < 0.025), 10q (P < 0.05), 11p (P < 0.01), 11q (P < 0.01), and 17p (P < 0.05), as well as the total number of aberrations (pTa grade 2: 4.1; pT1 grade 2: 8.6 aberrations per tumour). These data show characteristic chromosomal aberrations associated with invasion in superficial bladder cancer.

Carcinoma, Transitional Cell↗

PubMed1998

Metastatic retroperitoneal paraganglioma in a 16-year-old girl. Case report, molecular pathological and cytogenetic findings.

Retroperitoneal paraganglioma is a rare tumor, especially occurring in childhood and adolescence, with a marked tendency to become biologically malignant. It has not been possible to predict the clinical outcome of paraganglioma patients by conventional histology, hence malignancy can only be demonstrated by the occurrence of metastatic lesions. Currently, only limited information on the genetics of this tumor is available. We report on a 16-year-old girl with a large retroperitoneal paraganglioma and an osseous metastasis to the first lumbar vertebra. In addition to morphological and immunohistochemical examinations, a molecular cytogenetic analysis was performed. Comparative genomic hybridization (CGH) revealed imbalanced chromosomal aberrations with a loss of chromosome 1p and a gain of 1q, indicating isochromosome 1q. A loss of chromosome 3 as well as low-level gains of chromosomes 4, 5, 6q, 11q and 13q were detected. A PCR-based microsatellite analysis of 1p confirmed the loss of heterozygosity, including NB1 and NB2 putative tumor-suppressor gene regions. Telomerase activity, which is found in the majority of malignant tumors, could not be detected. The case presented here is the first more comprehensive molecular genetic analysis of a sporadic malignant paraganglioma.

Adolescent↗

PubMed1998

Comparative genomic hybridization and telomerase activity analysis identify two biologically different groups of 4s neuroblastomas.

Chromosomal aberrations of 20 stage 4s neuroblastomas were analysed by comparative genomic hybridization (CGH). In a subset of 13/20 tumours, telomerase activity was evaluated by the telomeric repeat amplification protocol (TRAP). The CGH data were compared with the CGH results of ten stage 1 and 2 (stage 1/2) and 22 stage 3 and 4 (stage 3/4) neuroblastomas. A total of 17/20 stage 4s neuroblastomas did not progress clinically, whereas tumour progression with lethal outcome occurred in 3/20 cases. The CGH data of clinically non-progressing stage 4s tumours revealed a high rate of whole-chromosome aberrations (73.4%) with an overrepresentation of mainly chromosomes 2, 6, 7, 12, 13, 17, 18 and an underrepresentation of mainly chromosomes 3, 4, 11, 14. MYCN amplification or 1p deletion was observed in only 1/27 or 2/17 clinically non-progressing stage 4s tumours respectively, whereas all three progressive stage 4s neuroblastomas showed MYCN amplification, 1p deletion and, in 2/3 cases, distal 17q gains. Except for one case, telomerase activity was not observed in non-progressing stage 4s neuroblastomas. In contrast, 4s tumours with lethal outcome revealed elevated telomerase activity levels. Our data suggest that stage 4s neuroblastomas belong to two biologically different groups, one of which displays the genetic features of localized stage 1/2 tumours, whereas the other mimics advanced stage 3/4 neuroblastomas.

Blotting, Southern↗

PubMed1998

[Comparative genomic hybridization (CGH) for detecting a heretofore undescribed amplified chromosomal segment in high-grade medullary osteosarcoma].

Osteosarcoma is one of the most commonly biopsied primary tumor of bone. High-grade osteosarcomas in particular exhibit a wide spectrum of cytogenetic changes. Molecular cytogenetic studies on osteosarcomas have shown that genomic amplification, especially of both the TP53-binding MDM2 gene and the flanking SAS gene, plays an important role in the biology of these tumors. We applied CGH in order to obtain a global view of DNA-sequence losses and gains in osteosarcoma. CGH was performed on 20 high-grade medullary osteosarcomas (13 primary tumors prior to chemotherapy, 5 tumors after chemotherapy, 2 established cell lines [MB63, HOS58]) using genomic DNA of snap-frozen tumor specimens. CGH revealed DNA copy number aberrations, mostly gains, in all the tumors studied with an average of 18.5 aberrations/tumor (range 8-32). High-level amplifications were observed in all cases (average 4.1 amplifications/tumor [range 1-10]). Amplicons affecting at least five tumors were mapped to 1p21-31 (9/20 cases), 3q25-qter (6/20), 6p12-21 (6/20), 8q12-qter (10/20), 12p11-12 (9/20), 12q12-15 (enclosing MDM2 and SAS loci, 7/20). Losses were most frequently seen at 3p, 10q, 11p and 13 (all 10/20). In conclusion, our CGH data indicated that genomic amplification plays an important role in the biology of osteosarcoma. CGH demonstrated the complexity of genetic aberrations in osteosarcomas. The detection of novel non-random DNA amplifications in our study has defined regions for further targeted molecular genetic research aimed at identifying those oncogenes that are characteristic of osteosarcoma development.

Bone Neoplasms↗

PubMed1998

[Evidence of genetic alterations in chromosome 11 in embryonal and alveolar rhabdomyosarcoma].

Various chromosome 11 alterations have been described in rhabdomyosarcoma (RMS). Allelic losses of 11p15.5 are characteristic of embryonal RMS (eRMS), whereas an increase in the expression of the Igf2 gene located on 11p15.5 has regularly been observed in eRMS and alveolar RMS (aRMS). The aim of our study was to analyse chromosome 11 alterations of RMS by combining different molecular-genetic and cytogenetic methods. 16 RMSs (7 aRMS with proven 2;13 or 1;13 translocations, 9 eRMS) were studied by a PCR-based microsatellite analysis of loci 11p15.5 and 11q23. Comparative genomic hybridization (CGH) was performed in 8/16 cases. The ploidy status of chromosome 11 was evaluated using the FISH technique. A RT-PCR analysis of Igf2 gene region was performed to evaluate the imprinting status. Allelic losses (LOH) of 11p15.5 were observed in 4/7 aRMS and 8/9 eRMS. These losses were accompanied by LOH of 11q23 in 2/7 aRMS and 5/9 eRMS, respectively. CGH of all the eRMSs and one aRMS studied revealed gains of genetic material mostly involving the entire length of chromosome 11. One aRMS showed a loss of chromosome 11 material, both in CGH and LOH analysis. In 2/9 aRMS, which neither in CGH nor in LOH analysis had exhibited chromosome 11 alterations, biallelic IGF-II expression was revealed. Our results show that chromosome 11 alterations play a major role in the biology of both alveolar and eRMS. Combining the data of our study, we demonstrated that three different chromosome 11 alterations are involved in the tumorigenesis of RMS: 1) LOH resulting in hemizygosity of chromosome 11. 2) LOH with simultaneous gains of chromosome 11 material due to uniparental polysomy. 3) loss of imprinting for the Igf2 gene in the absence of gross chromosome 11 alterations.

Chromosome Aberrations↗

PubMed1997

Comparison of DNA gains and losses in primary renal clear cell carcinomas and metastatic sites: importance of 1q and 3p copy number changes in metastatic events.

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.

Adenocarcinoma, Clear Cell↗

PubMed1997

Comparative genomic hybridization (CGH) analysis of neuroblastomas--an important methodological approach in paediatric tumour pathology.

Comparative genomic hybridization (CGH) was applied to 35 neuroblastomas to obtain a global view of genetic imbalances. Results were validated by means of Southern blot hybridization (detection of N-myc amplification), loss of heterozygosity (LOH) studies (detection of deletion 1p), and interphase cytogenetics [dual labelling fluorescence in situ hybridization (FISH) of centromeric 17 and erbB-2]. CGH allowed sensitive detection of N-myc amplification and chromosome 1p deletion, representing the most established prognostic markers of neuroblastoma. In addition, a high rate of chromosome 17 aberrations (63 per cent) with possible prognostic relevance was observed. Previously unreported high level copy number increases indicating oncogene amplification were mapped to chromosome subbands 2p13-14 and 3q24-26. Other recurrent regional chromosomal aberrations were localized on 11q, 12q, 13q, 14q, and 15q. CGH results were fully consistent with data of Southern blot analysis and LOH study, as well as interphase cytogenetics. These results show that CGH is a sensitive method for the detection of all prognostically relevant genetic alterations in neuroblastomas; that CGH considerably simplifies the detection of these alterations, resulting in a single methodological approach; and that CGH is a powerful tool to elucidate previously unknown genetic changes in neuroblastomas.

Blotting, Southern↗

PubMed1996

[Comparative genomic hybridization in pathology. A new molecular cytogenetic method].

Comparative genomic hybridisation (CGH) is a new cytogenetic method, which is based on a combination of fluorescence microscopy and digital image analysis. The molecular genetic basis is the hybridization of a mixture of fluorescein labeled test-DNA and reference-DNA on normal metaphase chromosomes. Comparative analysis allows the identification of all unbalanced chromosomal aberrations of the test-DNA in a single experimental step. The resulting DNA gains or DNA losses on the chromosomal or subchromosomal level mirror possible amplifications of oncogenes or losses of suppress orgenes. As CGH can be performed with genomic DNA of formalin-fixed and fresh-frozen tissue or cells, this new method is a very effective tool for pathologists and cytologists in the extended genomic screening of tumors and genetically altered tissues. Despite CGH analysis at present is restricted to research applications; its widespread dissemination as a routine method in diagnostic pathology can be expected in the near future.

Animals↗

PubMed1996

[Synopsis of unbalanced chromosome aberrations in neuroblastoma by comparative genomic hybridization].

Neuroblastoma is the most frequent extracranial solid tumor of early childhood. Histologically and genetically, neuroblastoma represents a heterogeneous group of tumors with significant differences in clinical behavior. In the past, several different characteristic chromosomal aberrations of neuroblastoma have been described, of which a deletion on chromosome 1p and N-myc amplification have been shown to be of major prognostic significance. However, the role of various other nonrandom DNA imbalances in tumor development and progression needs to be clarified. Taking advantage of the recently established comparative genomic hybridization (CGH), we show that this method is able to accurately detect chromosomal imbalances of known prognostic impact. As CGH gives a comprehensive picture of genetic imbalances in just one experiment, it additionally sheds light on other abnormalities of possible prognostic relevance. We therefore recommend further use of this method not only in the field of research but also for the purpose of genetic routine diagnostics in neuroblastoma.

Child↗

PubMed1989

[Asbestos screening of autopsy material].

UNLABELLED: This study was designed to provide basic data on the deposition of asbestos in human tissue in an urban area (Hamburg) with increased immission rates of fibres. The analysis of the unselected autopsy cases was carried out by light microscopy counting the typical asbestos bodies (method: wet digestion of tissue and filter technique). - RESULTS: a) The average concentration of asbestos bodies (AB) per ccm lung tissue (n = 80) amounts to 35 AB/ccm (men 38 AB/ccm, females 15 AB/ccm). b) Asbestos bodies could be found regularly in extrapulmonary tissues (n = 20, up to 13 different tissue samples per case), most frequently in lymph nodes, thyroid gland and spleen. c) Lungs of children in the age of 7 to 16 years (n = 40) showed asbestos bodies in 35% of the examined cases (with a range from 3 to 31 AB/ccm lung tissue).

Adolescent↗

PubMedDate not supplied

[Surgical reconstruction of fibrous dysplasia of bone in long-term follow-up].

PURPOSE: To examine how different operative measures influence the surgical outcome in patients with fibrous dysplasia of bone. METHODS: 118 dysplastic fibrous lesions of bone were surgically treated and reviewed in 70 patients between 1983 to 1993 (eleven years) with a median follow-up of six and a half years. Surgery consisted of intralesional curettage in 93 and marginal en bloc resection in 25 lesions. Bony defects were reconstructed with autogenous iliac crest graft in 55 lesions, with autogenous fibula graft in 9, with homologous bone chips in 28, and 5 times with a homologous fibula graft from the bone bank. In 33 lesions the entire defect was filled with polymethylmethacrylate. Osteosynthesis was performed in 41 patients. RESULTS: Recurrences requiring surgical revision were observed in 26 of 74 primary lesions (= 35% overall recurrence rate) at a mean 123.6 weeks postoperatively. The most frequent primary and recurrence location was the proximal femur (85% revision rate). 69% of all recurrences occurred under the age of 20. After intralesional curettage the reoperation rate was 32% and after marginal resection 8%. After reconstruction with autogenous iliac crest graft recurrence rate was 36%, after autogenous fibula graft 55%, after homologous bone chips 18%, after polymethylmethacrylate 9% and allograft fibula reconstruction showed no recurrences. A combined stable osteosynthesis bridging the fibrous osseous defect significantly reduced the revision rate to 3% (p = 0.01). CONCLUSION: Intralesional curettage and reconstruction with autogenous iliac crest graft in fibrous dysplasia of bone leads to a high recurrence rate. Reconstruction with cortical grafts or bone chips from the bone bank, if necessary in combination with a durable osteosynthesis in mechanically demanding locations, or solely bone cement in mechanically less demanding areas, reduces the revision rate in patients with monoostotic and polyostotic fibrous dysplasia.

Adolescent↗

PubMedDate not supplied

Periosteal chondroma: MR characteristics.

PURPOSE: The purpose of this study was to describe the MR characteristics of periosteal chondroma. METHOD: MR images of 12 proven cases of periosteal chondroma were analyzed with reference to tumor morphology and size. MR features were correlated with radiographic and pathologic findings. RESULTS: Tumor size ranged from 1 to 7 cm in maximum diameter with a mean value of 2.6 cm. On MR images, a soft tissue mass at the bone surface with pressure erosion of adjacent cortical bone could be identified in all cases. All lesions were bordered by a hypointense rim (100%) and frequently showed a lobulated configuration (75%). Edema of medullary bone or soft tissues was not observed in any of the cases. Signal intensity of cartilaginous tumor tissue was typically hypo-or isointense relative to muscle on T1-weighted (100%) and hyperintense relative to fat on T2-weighted (92%) and T2*-weighted (100%) MR images. Radiographically significant calcifications of the tumor matrix, present in half of the cases, caused focal signal loss on MR images of all pulse sequences. Contrast enhancement was observed predominantly at the periphery of the lesions (100%), which on pathologic examinations typically contained fibrovascular bundles, surrounding the cartilage lobules. CONCLUSION: Periosteal chondroma appears to have a relatively typical MR appearance, which reflects the histologic composition of the lesion. In addition to radiography, MRI therefore can substantially aid in the preoperative diagnosis of this rare bone lesion.

Adolescent↗