Biological importance of a polymorphic CA sequence within intron 1 of the epidermal growth factor receptor gene (EGFR) in high grade central osteosarcomas.

TY - JOUR

T1 - Biological importance of a polymorphic CA sequence within intron 1 of the epidermal growth factor receptor gene (EGFR) in high grade central osteosarcomas.

AU - Kersting, Christian

AU - Agelopoulos, Konstantin

AU - Schmidt, Hartmut

AU - Korsching, Eberhard

AU - August, Christian

AU - Gosheger, Georg

AU - Dirksen, Uta

AU - Juergens, Heribert

AU - Winkelmann, Wilfried

AU - Brandt, Burkhard

AU - Bielack, Stefan

AU - Buerger, Horst

AU - Gebert, Carsten

PY - 2008

Y1 - 2008

N2 - Expression of EGFR in high grade osteosarcomas has been observed to be correlated with an improved prognosis. Yet, the underlying mechanism remained unclear since amplifications of EGFR have rarely been described. Recently, the length of a polymorphic CA repeat located at a 5'-regulatory sequence in the intron 1 of the EGFR gene (SSR I) has been shown to be associated with its basal transcriptional activity. We therefore determined the allelic length of CA SSR-I in 219 cases of high grade osteosarcoma and correlated the results with EGFR expression in 34 cases, the presence of amplifications within the CA SSR-I repeat in 59 cases, and clinical follow-up. Our results confirm that in osteosarcoma patients short alleles are more frequent than longer ones, 16 CA repeats being the most frequent. The allele composition differed significantly from the one recently described in a healthy control population (P <0.01). Short alleles tended to be associated with increased expression of EGFR. Amplifications of the EGFR gene were seen in 13.5% of cases. Significant correlations between allele length composition and neoadjuvant chemotherapy response or long term clinical outcome could not be established. While we were able to show that high frequency of EGFR expression in osteosarcomas is associated with predominantly short alleles of EGFR-CA SSR I, persisting shortcomings in the correspondence with clinical data point toward the existence of additional, putatively more important transcription control mechanisms for EGFR in osteosarcomas which might account for the good prognostic value of EGFR expression.

AB - Expression of EGFR in high grade osteosarcomas has been observed to be correlated with an improved prognosis. Yet, the underlying mechanism remained unclear since amplifications of EGFR have rarely been described. Recently, the length of a polymorphic CA repeat located at a 5'-regulatory sequence in the intron 1 of the EGFR gene (SSR I) has been shown to be associated with its basal transcriptional activity. We therefore determined the allelic length of CA SSR-I in 219 cases of high grade osteosarcoma and correlated the results with EGFR expression in 34 cases, the presence of amplifications within the CA SSR-I repeat in 59 cases, and clinical follow-up. Our results confirm that in osteosarcoma patients short alleles are more frequent than longer ones, 16 CA repeats being the most frequent. The allele composition differed significantly from the one recently described in a healthy control population (P <0.01). Short alleles tended to be associated with increased expression of EGFR. Amplifications of the EGFR gene were seen in 13.5% of cases. Significant correlations between allele length composition and neoadjuvant chemotherapy response or long term clinical outcome could not be established. While we were able to show that high frequency of EGFR expression in osteosarcomas is associated with predominantly short alleles of EGFR-CA SSR I, persisting shortcomings in the correspondence with clinical data point toward the existence of additional, putatively more important transcription control mechanisms for EGFR in osteosarcomas which might account for the good prognostic value of EGFR expression.

M3 - SCORING: Zeitschriftenaufsatz

VL - 47

SP - 657

EP - 664

JO - GENE CHROMOSOME CANC

JF - GENE CHROMOSOME CANC

SN - 1045-2257

IS - 8

M1 - 8

ER -