1/7. Multifocal osteosarcoma as second tumor after childhood retinoblastoma.We present a case of multifocal osteosarcoma (MFOS) arising 11.5 years after successful treatment of bilateral retinoblastoma. The clinical, imaging and pathological findings at onset, after therapy, and during follow-up are described. Fluorescent in situ hybridization did not reveal a deletion of the RB-1 retinoblastoma gene, although the presence of an inactivating mutation invisible to this method cannot be ruled out. The MFOS may have been a second multifocal tumor associated with the original retinoblastoma or a post-irradiation sarcoma with extensive metastases.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/7. Primary pulmonary osteosarcoma: case report and molecular analysis.BACKGROUND: Primary pulmonary osteosarcoma is an extremely rare malignancy. To date, only 12 cases have been reported, with a high mortality rate. The authors report on a newly diagnosed patient and describe investigations that were performed using immunohistochemistry and comparative genomic hybridization (CGH). methods: The clinical course of a woman age 37 years is presented. Along with routine histologic examination, immunohistochemistry was used to demonstrate differentiation-associated proteins, oncoproteins, and other markers; CGH analysis for genomic alterations; and histochemistry to demonstrate alkaline phosphatase activity. RESULTS: Immunohistochemical analysis showed varying expression patterns using antibodies against a panel of tumor markers. Most notable was high overexpression of BCL-2 and cyclin d. CGH analysis showed that this neoplasm contained a much higher level of genetic aberrations compared with skeletal osteosarcoma. CONCLUSIONS: This tumor exhibited features common to skeletal osteosarcomas but also had some unique features. genome analysis suggests that this tumor has several genetic aberrations in common with extraskeletal osteosarcoma. The novel regions of instability identified within the tumor genome may contribute toward the unique tumor phenotype and relative chemoresistance.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
3/7. Dedifferentiation of a well-differentiated liposarcoma to a highly malignant metastatic osteosarcoma: amplification of 12q14 at all stages and gain of 1q22-q24 associated with metastases.Well-differentiated liposarcomas (WDLPS), especially those located in the retroperitoneum, may occasionally undergo dedifferentiation. Although this process is associated with a more aggressive clinical course, dedifferentiated liposarcomas rarely produces metastases. The case reported here is rather uncommon: A retroperitoneal WDLPS gave lung metastases that were diagnosed as highly malignant osteosarcomas. We used comparative genomic hybridization (CGH), fluorescence in situ hybridization (FISH), and Southern blot analyses to characterize the copy number changes and genetic aberrations occurring at different stages of the disease. In the primary tumor, the only detectable aberration was amplification of 12q13-q14, which was present only in a fraction of the cells and revealed by FISH analysis. High-level amplification of 12q13-q14, involving CDK4, MDM2, and HMGIC, was seen both in the relapse and the metastases. The second most common change, gain or high-level amplification of 1q22-q24, was detectable by CGH only in the osteogenic metastases, as was loss of the distal 2q. FISH analyses revealed considerable heterogeneity in the samples, and the percentage of cells showing aberrations was significantly higher in the metastatic samples. In particular, increased copy numbers of 789f2, a marker for 1q21 amplification in sarcomas, was observed in more than 65% of the cells in the metastatic samples, but in less than 10% of the cells from the recurrent samples. These observations could indicate that 1q amplification, in particular, may be indicative of a more malignant phenotype and ability of metastasis in WDLPS, as has also been suggested by others.- - - - - - - - - - ranking = 2keywords = hybridization (Clic here for more details about this article) |
4/7. osteosarcoma in a patient with McCune-Albright syndrome and Mazabraud's syndrome: a case report emphasizing the cytological and cytogenetic findings.Osteosarcomatous transformation in fibrous dysplasia is unusual. The incidence is increased in patients with concomitant Mazabraud's syndrome and McCune-Albright syndrome. We report the cytological, histological, and cytogenetic findings of this rare entity arising from a mass in the right elbow of a 44-year-old African-American woman. The fine-needle aspiration (FNA) findings were diagnostic of malignancy, with markedly atypical spindle and polygonal cells admixed with osteoid. The diagnosis of osteosarcoma by FNA was subsequently further confirmed by histological evaluation of an above-elbow amputation specimen. fluorescence in situ hybridization and comparative genomic hybridization demonstrated trisomies of chromosomes 5 and 7 in the fibrous dysplasia and osteosarcoma. In addition, multiple chromosomal abnormalities were also noted in the osteosarcoma. We are unaware of any previous reports of the cytogenetic findings in the tissue of this rare condition, and argue for the value of FNA in the evaluation of such patients under selected conditions.- - - - - - - - - - ranking = 2keywords = hybridization (Clic here for more details about this article) |
5/7. CGH evaluation of two de novo synchronous tumors in a child with a germline p53 mutation.We report the case of a child who developed two de novo synchronous tumors: an osteosarcoma and an embryonal rhabdomyosarcoma. The patient was determined to be a de novo carrier of a P53 germline mutation. comparative genomic hybridization (CGH) analysis revealed that each of the neoplasms was characterized by a specific set of chromosomal imbalances and high-level amplification (HLA) regions. Our CGH findings provide evidence that cancer development is a cellular/organ specific event.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
6/7. Monoallelic deletion of the p53 gene through chromosomal translocation in a small cell osteosarcoma.Small cell osteosarcoma is a rare bone tumor of high-grade malignancy that most often arises in the metaphysis of long bones in the second decade of life. Cytogenetic and molecular genetic findings in small cell osteosarcoma are poorly defined. Conventional cytogenetic analysis of a small cell osteosarcoma arising in the proximal tibia of a 9-year-old male revealed a diploid chromosomal complement with complex structural rearrangements involving chromosomes 6, 16, and 17. Immunohistochemical assessment of p53 protein expression revealed nuclear p53 immunoreactivity in approximately 15% of the neoplastic cells. Subsequent fluorescence in situ hybridization (FISH) analyses confirmed loss of the p53 gene locus on the derivative chromosome 17 homolog and were negative for amplification of the MDM2, CDK4, c-MYC, HER-2/neu, CCND1, and COPS3 gene loci. To the best of our knowledge, this represents the first demonstration of monoallelic deletion of p53 in small cell osteosarcoma, suggesting that p53 alterations may play an important role in the development of small cell osteosarcoma as well as conventional osteosarcoma.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
7/7. Isolation of osteosarcoma-associated amplified dna sequences using representational difference analysis.comparative genomic hybridization analysis of a primary osteosarcoma and its metastasis revealed two regions of dna amplification, one at 17p11.2-12 and one at 19q12-13. Subsequent representational difference analysis of the primary tumor resulted in the isolation of two distinct tumor-amplified dna fragments originating from chromosome 19. A YAC clone corresponding to one of the two isolated dna fragments was used for fluorescence in situ hybridization on normal human lymphocyte metaphases and tumor-derived nuclei. This resulted in the localization of this YAC to 19q12-13.1 and confirmed the amplification status of the isolated fragment in the tumors. The availability of such RDA-isolated sequences may be instrumental in the search for genes relevant for tumor development.- - - - - - - - - - ranking = 2keywords = hybridization (Clic here for more details about this article) |