title: Multimodal genetic diagnosis of solid variant alveolar rhabdomyosarcoma.
abstract: 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.
authors.affiliation: Department of Genetics, Portuguese Oncology Institute, Porto, Portugal.
authors.forename: Nuno
authors.initials: N
authors.lastname: Cerveira
authors.forename: Lurdes
authors.initials: L
authors.lastname: Torres
authors.forename: Franclim R
authors.initials: FR
authors.lastname: Ribeiro
authors.forename: Rui
authors.initials: R
authors.lastname: Henrique
authors.forename: Armando
authors.initials: A
authors.lastname: Pinto
authors.forename: Susana
authors.initials: S
authors.lastname: Bizarro
authors.forename: Ana M
authors.initials: AM
authors.lastname: Ferreira
authors.forename: Carlos
authors.initials: C
authors.lastname: Lopes
authors.forename: Manuel R
authors.initials: MR
authors.lastname: Teixeira
mesh_terms: D001483:Base Sequence; D002675:Child, Preschool; D002871:Chromosome Banding; D002878:Chromosomes, Human, Pair 1; D002882:Chromosomes, Human, Pair 13; D002889:Chromosomes, Human, Pair 2; D017931:DNA Primers; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics; D006801:Humans; D007621:Karyotyping; D008297:Male; D009693:Nucleic Acid Hybridization; D000072041:PAX3 Transcription Factor; D051763:PAX7 Transcription Factor / Q000235:genetics; D051761:Paired Box Transcription Factors / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018232:Rhabdomyosarcoma, Alveolar / Q000175:diagnosis* / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: D017931:DNA Primers; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051763:PAX7 Transcription Factor; C497321:PAX7 protein, human; D051761:Paired Box Transcription Factors; D012333:RNA, Messenger