Frequent genomic abnormalities at TWIST in human pediatric osteosarcomas.
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.
Entz-Werlé
Natacha
N
Service de pédiatrie Onco-Hématologie, CHRU Hautepierre, Strasbourg, France. Natacha.Entz-werle@chru-strasbourg.fr
Stoetzel
Corinne
C
Berard-Marec
Perrine
P
Kalifa
Chantal
C
Brugiere
Laurence
L
Pacquement
Hélène
H
Schmitt
Claudine
C
Tabone
Marie-Dominique
MD
Gentet
Jean-Claude
JC
Quillet
Robert
R
Oudet
Pierre
P
Lutz
Patrick
P
Babin-Boilletot
Annie
A
Gaub
Marie-Pierre
MP
Perrin-Schmitt
Fabienne
F
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
D005819:Genetic Markers; D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1