title: Frequent genomic abnormalities at TWIST in human pediatric osteosarcomas.
abstract: The identification of genes as markers for chromosome aberrations in specific tumors might facilitate oncogenesis mechanism comprehension, cancer detection, prediction of clinical outcomes, and response to therapy. Previous physiologic and oncologic data identified the TWIST gene as a marker for mesodermal derivative and bone tissue differentiation, but its contribution to bone malignancies has not been investigated. In the present study, search for genomic alterations in high-grade pediatric osteosarcomas was focused on the 7p21 region, and more specifically on the TWIST gene. In a cohort of 74 patients, we observed by allelotyping that 31 of 68 informative tumors were rearranged at the TWIST locus. Among them, analysis by quantitative PCR (QPCR) revealed that, surprisingly, mostly deletions (22/68), but also amplifications (9/68), of the TWIST gene were detected. Furthermore, deletions at TWIST were statistically correlated to other molecular abnormalities, like alterations at the APC or c-kit loci, as well as to clinical features such as a poor outcome. This work shows that the TWIST gene seemed to be involved in high-grade pediatric osteosarcomas and is a new marker with a possible initial predictive value.
authors.affiliation: Service de pédiatrie Onco-Hématologie, CHRU Hautepierre, Strasbourg, France. Natacha.Entz-werle@chru-strasbourg.fr
authors.forename: Natacha
authors.initials: N
authors.lastname: Entz-Werlé
authors.forename: Corinne
authors.initials: C
authors.lastname: Stoetzel
authors.forename: Perrine
authors.initials: P
authors.lastname: Berard-Marec
authors.forename: Chantal
authors.initials: C
authors.lastname: Kalifa
authors.forename: Laurence
authors.initials: L
authors.lastname: Brugiere
authors.forename: Hélène
authors.initials: H
authors.lastname: Pacquement
authors.forename: Claudine
authors.initials: C
authors.lastname: Schmitt
authors.forename: Marie-Dominique
authors.initials: MD
authors.lastname: Tabone
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Gentet
authors.forename: Robert
authors.initials: R
authors.lastname: Quillet
authors.forename: Pierre
authors.initials: P
authors.lastname: Oudet
authors.forename: Patrick
authors.initials: P
authors.lastname: Lutz
authors.forename: Annie
authors.initials: A
authors.lastname: Babin-Boilletot
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Gaub
authors.forename: Fabienne
authors.initials: F
authors.lastname: Perrin-Schmitt
mesh_terms: D000293:Adolescent; D000328:Adult; D001859:Bone Neoplasms / Q000235:genetics* / Q000401:mortality; D001842:Bone and Bones / Q000473:pathology; D002454:Cell Differentiation; D002648:Child; D002675:Child, Preschool; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008648:Mesoderm / Q000473:pathology; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D012516:Osteosarcoma / Q000235:genetics* / Q000401:mortality; D016019:Survival Analysis; D014157:Transcription Factors / Q000235:genetics*; D051879:Twist-Related Protein 1
chemical_list: D005819:Genetic Markers; D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1