title: Cytogenetic and molecular findings related to rhabdomyosarcoma. An analysis of seven cases.
abstract: Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in childhood. Histologically, it is subdivided histologically into two main subtypes: alveolar (ARMS) and embryonal (ERMS). ARMS is characterized by t(2;13)(q35;q14) or its variant t(1;13)(p36;q14), which fuse PAX3 and PAX7, respectively, with FKHR to produce chimeric genes. ERMS is frequently associated with loss of heterozygosity of 11p15.5. We investigated seven RMS (three ARMS and four ERMS) by means of cytogenetic, fluorescence in situ hybridization, and molecular analyses, including the study of the main genes implicated in the G1- to S-phase cell cycle transition, and correlated these studies with pathologic findings and clinical outcome. All tumors showed clonal, numerical, and structural chromosomal abnormalities. Two ARMS had the t(2;13)(q35;q14) and the third a PAX7/FKHR fusion, a cryptic t(1;13)(p36;q14), undetected by cytogenetic techniques, but revealed by reverse transcriptase polymerase chain reaction. One ERMS showed a der(11)t(3;11)(p21;p15) as a sole structural anomaly. Gene amplification was seen in four tumors, as double minutes or in the form of homogeneously staining regions. Overexpression of MYCN oncogene was found in two ARMS; N-myc DNA probe detected oncogene amplification located on the double minutes of these cases. Analysis of the regulatory genes responsible for G1- to S-phase transition showed a homozygous deletion of the 9p21 locus genes in a spindle-cell ERMS.
authors.affiliation: Department of Pathology, Medical School, University of Valencia, Avda. Blasco Ibáñez 17, Valencia 46010, Spain.
authors.forename: Rosario
authors.initials: R
authors.lastname: Gil-Benso
authors.forename: Concha
authors.initials: C
authors.lastname: López-Ginés
authors.forename: Carmen
authors.initials: C
authors.lastname: Carda
authors.forename: José Antonio
authors.initials: JA
authors.lastname: López-Guerrero
authors.forename: Jaime
authors.initials: J
authors.lastname: Ferrer
authors.forename: Antonio
authors.initials: A
authors.lastname: Pellín-Pérez
authors.forename: Antonio
authors.initials: A
authors.lastname: Llombart-Bosch
mesh_terms: D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D016259:Genes, myc; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D000072041:PAX3 Transcription Factor; D051763:PAX7 Transcription Factor; D051761:Paired Box Transcription Factors; D012208:Rhabdomyosarcoma / Q000235:genetics* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051763:PAX7 Transcription Factor; C497321:PAX7 protein, human; D051761:Paired Box Transcription Factors; D014157:Transcription Factors; C068686:Pax3 protein, mouse