1/5. Solid variant of alveolar rhabdomyosarcoma with unbalanced t(2;13) and hypotetraploidy, without MYCN amplification.The histological subtype of alveolar rhabdomyosarcoma (AR) is characterised by the cytogenetic translocation t(2;13)(q35;q14) in approximately 70% of cases, a rearrangement rarely present in the embryonal rhabdomyosarcoma (ER) subtype. The MYCN gene is amplified in some cases of AR. We present a young man with an unusual pattern, namely solid variant of AR with hypotetraploidy and the t(2;13) in an unbalanced form. The MYCN gene was not amplified on FISH, but showed increased copy number, consistent with ploidy.- - - - - - - - - - ranking = 1keywords = amplification (Clic here for more details about this article) |
2/5. Multimodal genetic diagnosis of solid variant alveolar rhabdomyosarcoma.The most common types of rhabdomyosarcoma (RMS) are alveolar RMS (ARMS), which are characterized by the specific translocation t(2;13)(q35;q14) or its rarer variant, t(1;13)(p36;q14), producing the fusion genes PAX3-FKHR and PAX7-FKHR, respectively, and embryonal RMS (ERMS), which is characterized by multiple numeric chromosome changes. A solid variant of ARMS that is morphologically indistinguishable from ERMS has been described recently. We present two cases with an initial histopathologic diagnosis of ERMS in which the combined findings by cytogenetic, reverse-transcriptase polymerase chain reaction (RT-PCR), and comparative genomic hybridization (CGH) analyses demonstrate that both tumors were in fact the solid variant of ARMS. The cytogenetic analysis of patient 1 revealed a t(2;13)(q35;q14) and the RT-PCR study detected the corresponding PAX3-FKHR chimeric transcript. In patient 2, the cytogenetic finding of multiple trisomies was compatible with the initial histopathologic diagnosis of ERMS, but the finding of a PAX7-FKHR fusion transcript by RT-PCR pointed to the diagnosis of ARMS. Interestingly, the CGH findings of this case reconciled the molecular and cytogenetic data by detecting, in addition to the trisomies, amplification of chromosomal bands 1p36 and 13q14, where the PAX7 and FKHR genes are located, respectively. Our data indicate that this multimodal genetic analysis could be important for the differential diagnosis of these tumors. Furthermore, our findings and previous studies indicate that there are no apparent genetic differences between solid variant and typical ARMS.- - - - - - - - - - ranking = 0.25keywords = amplification (Clic here for more details about this article) |
3/5. MDM2 amplification in a primary alveolar rhabdomyosarcoma displaying a t(2;13)(q35;q14).This report describes a case of rhabdomyosarcoma associated with a 2;13 translocation and multiple double minute chromosomes. The origin of the amplified dna was identified using comparative genomic hybridization, which pinpointed a unique spot at 12q13-->q14. Band 12q13 has been shown to contain several genes that are occasionally amplified in other sarcomas. Fluorescene in situ hybridization to tumor metaphases with probes specific for this region indicated that the double minutes contained the MDM2 gene but not the CDK4 gene. MDM2 amplification was further quantified by Southern hybridization, which showed a mean value of 25 copies per haploid genome. This is the first example of MDM2 amplification in a rhabdomyosarcoma.- - - - - - - - - - ranking = 1.5keywords = amplification (Clic here for more details about this article) |
4/5. Novel formation and amplification of the PAX7-FKHR fusion gene in a case of alveolar rhabdomyosarcoma.Alveolar rhabdomyosarcomas frequently exhibit specific translocations, resulting in the fusion of the FKHR gene at 13q14 with either the PAX3 or PAX7 gene at 2q35 and 1p36, respectively. comparative genomic hybridization revealed amplification at 13q14 and 1p36, suggesting amplification of the PAX7-FKHR fusion gene in two cases of alveolar rhabdomyosarcoma. A PAX7-FKHR fusion transcript was demonstrated in both cases by reverse transcription-polymerase chain reaction followed by sequence analysis. In one case, amplification of the PAX7 gene and 3'-and 5'-FKHR gene sequences was demonstrated by using interphase fluorescence in situ hybridization on tumor imprints. The colocalization, variable copy number, and distribution of signals from the three cosmids was consistent with amplification of these sequences on double minutes, which were present cytogenetically. chromatin release studies suggested that the amplified sequences correlated with amplification of the PAX7-FKHR fusion gene which resulted from the insertion of PAX7 sequences into the first intron of FKHR gene, in keeping with the absence of cytogenetic evidence for derivative chromosomes.- - - - - - - - - - ranking = 2.25keywords = amplification (Clic here for more details about this article) |
5/5. Solid alveolar rhabdomyosarcoma of the thorax in a child.AIMS: This case illustrates the difficulties and pitfalls of diagnosis of alveolar rhabdomyosarcoma in its solid variant and in an unusual primary location, the mediastinum. CASE DETAILS: A 9-year-old boy presented with a primary thoracic tumour associated with metastasis in the left sacroiliac joint. Bronchial and mediastinal biopsies showed a malignant neoplasm with a solid sheet-like pattern of small round cells with a high nuclear to cytoplasmic ratio associated with little or no fibrosis usually evocative of a peripheral neuroectodermal tumour (PNET) at this age. Immunohistochemical positive staining with vimentin (80% of tumour cells), desmin (20%) and titin (30%) antibodies was suggestive of a rhabdomyosarcoma. In addition, all neural cell adhesion molecule (NCAM) markers tested were positive as well as MIC2, a marker for the Ewing family of sarcomas. There was no rhabdomyoid differentiation at ultrastructural examination. Molecular analysis with RT-PCR amplification of rna isolated from the tumour demonstrated the presence of a PAX3/FKHR fusion transcript, product of a t(2;13) reciprocal translocation, a genetic marker specific for alveolar rhabdomyosarcoma. CONCLUSIONS: The diagnostic methodology of a small round cell tumour of the child must now include immunohistochemical study and molecular biology to confirm the diagnosis of alveolar rhabdomyosarcoma, in a solid and undifferentiated variant.- - - - - - - - - - ranking = 0.25keywords = amplification (Clic here for more details about this article) |