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Genetic alterations in primary osteosarcoma from 54 children and adolescents by targeted allelotyping.

Entz-Werle N, Schneider A, Kalifa C, Voegeli AC, Tabone MD, Marec-Berard P, Marcellin L, Pacquement H, Terrier P, Boutard P, Meyer N, Gaub MP, Lutz P, Babin A, Oudet P - Br. J. Cancer (2003)

Bottom Line: Microsatellites investigating Rb, p53 and the 9p21 region were particularly altered without a significant correlation with prognosis.In conclusion, this panel allowed us to characterise paediatric osteosarcomas.Correlation of prognosis with the altered 7q31 region could be a useful tool and further studies are required to confirm the importance of 5q21.

View Article: PubMed Central - PubMed

Affiliation: Service de Biochimie et Biologie Moléculaire, CHRU Hautepierre, Avenue Molière, 67098 Strasbourg Cedex, France. Natacha.Entz-werle@chru-strasbourg.fr

ABSTRACT
At present, the only recognised prognostic factor for primary osteosarcoma is the histological response to preoperative chemotherapy. Our study was designed to identify new diagnostic markers that could eventually have a prognostic value. A total of 54 patients under 20 years of age with primary osteosarcomas were studied while under treatment by the French Society of Paediatric Oncology OS 94 protocol. Paired normal and biopsy samples were collected. In addition, surgical resection specimens, following preoperative chemotherapy, were obtained in 13 cases. After genomic DNA extraction, an allelotyping analysis targeting microsatellites linked to Rb and p53 genes, and 9p21, 7q31 and 5q21 regions was performed. In all, 94% of the samples at diagnosis showed allelic imbalance and the biopsies were highly rearranged except for the microsatellite targeting 7q31. The same panel was highly informative at surgical resection. Microsatellites investigating Rb, p53 and the 9p21 region were particularly altered without a significant correlation with prognosis. On the other hand, the alteration of the 7q31 locus at diagnosis was significantly correlated with a worse prognosis and a new frequently altered locus, 5q21, was described. In conclusion, this panel allowed us to characterise paediatric osteosarcomas. Correlation of prognosis with the altered 7q31 region could be a useful tool and further studies are required to confirm the importance of 5q21.

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Related in: MedlinePlus

Kaplan–Meier EFS curve for the PR with AI at 5q21 region and without alterations. This statistical analysis showed a trend between the presence of AI and a worse survival.
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fig5: Kaplan–Meier EFS curve for the PR with AI at 5q21 region and without alterations. This statistical analysis showed a trend between the presence of AI and a worse survival.

Mentions: Kaplan–Meier EFS curves of the microsatellite analysis at 7q31 locus for the entire population (A) and for the PR (B) with a statistically significant association between the presence of AI and a worse prognosis (——).


Genetic alterations in primary osteosarcoma from 54 children and adolescents by targeted allelotyping.

Entz-Werle N, Schneider A, Kalifa C, Voegeli AC, Tabone MD, Marec-Berard P, Marcellin L, Pacquement H, Terrier P, Boutard P, Meyer N, Gaub MP, Lutz P, Babin A, Oudet P - Br. J. Cancer (2003)

Kaplan–Meier EFS curve for the PR with AI at 5q21 region and without alterations. This statistical analysis showed a trend between the presence of AI and a worse survival.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2741103&req=5

fig5: Kaplan–Meier EFS curve for the PR with AI at 5q21 region and without alterations. This statistical analysis showed a trend between the presence of AI and a worse survival.
Mentions: Kaplan–Meier EFS curves of the microsatellite analysis at 7q31 locus for the entire population (A) and for the PR (B) with a statistically significant association between the presence of AI and a worse prognosis (——).

Bottom Line: Microsatellites investigating Rb, p53 and the 9p21 region were particularly altered without a significant correlation with prognosis.In conclusion, this panel allowed us to characterise paediatric osteosarcomas.Correlation of prognosis with the altered 7q31 region could be a useful tool and further studies are required to confirm the importance of 5q21.

View Article: PubMed Central - PubMed

Affiliation: Service de Biochimie et Biologie Moléculaire, CHRU Hautepierre, Avenue Molière, 67098 Strasbourg Cedex, France. Natacha.Entz-werle@chru-strasbourg.fr

ABSTRACT
At present, the only recognised prognostic factor for primary osteosarcoma is the histological response to preoperative chemotherapy. Our study was designed to identify new diagnostic markers that could eventually have a prognostic value. A total of 54 patients under 20 years of age with primary osteosarcomas were studied while under treatment by the French Society of Paediatric Oncology OS 94 protocol. Paired normal and biopsy samples were collected. In addition, surgical resection specimens, following preoperative chemotherapy, were obtained in 13 cases. After genomic DNA extraction, an allelotyping analysis targeting microsatellites linked to Rb and p53 genes, and 9p21, 7q31 and 5q21 regions was performed. In all, 94% of the samples at diagnosis showed allelic imbalance and the biopsies were highly rearranged except for the microsatellite targeting 7q31. The same panel was highly informative at surgical resection. Microsatellites investigating Rb, p53 and the 9p21 region were particularly altered without a significant correlation with prognosis. On the other hand, the alteration of the 7q31 locus at diagnosis was significantly correlated with a worse prognosis and a new frequently altered locus, 5q21, was described. In conclusion, this panel allowed us to characterise paediatric osteosarcomas. Correlation of prognosis with the altered 7q31 region could be a useful tool and further studies are required to confirm the importance of 5q21.

Show MeSH
Related in: MedlinePlus