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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

Allelic imbalance (AI) frequencies and percentages of normal (N) status at the five targeted loci in the different subgroups of patients: GR, PR and the population combining different events such as partial remission, relapse and deaths (event).
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fig3: Allelic imbalance (AI) frequencies and percentages of normal (N) status at the five targeted loci in the different subgroups of patients: GR, PR and the population combining different events such as partial remission, relapse and deaths (event).

Mentions: A high level of AI frequency was observed at each locus, except for the microsatellite targeting 7q31. Taking into account heterozygous loci, AI was found in 83% (29 out of 35) for TP53, 71% (27 out of 38) for RB1, 66% (23 out of 35) for D9S171, 34% (11 out of 32) for D7S486 and 58% (26 out of 45) for D5S346 and D5S492 (Table 1). Furthermore, a slightly higher proportion of homozygous loci, than reported in the database, was observed at D7S486 (41 vs 35% for TP53, 30% for RB1, 35% for D9S171 and 17% for 5q21). At least one of the cell cycle genes, p53, Rb or locus 9p21, was altered in 88% biopsies. In order to analyse the data at the locus containing APC, we used two microsatellites flanking this region (D5S346 and D5S492), and considered this locus as informative if it was heterozygous for both markers or if at least one of the two markers was modified, and the second one noninformative. In cases where both microsatellites (D5S346 and D5S492) were informative, results at both sites were always identical, either both AI or both normal. In GR and PR subgroups, AI frequencies for each microsatellite did not show statistical differences (Figure 3Figure 3


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)

Allelic imbalance (AI) frequencies and percentages of normal (N) status at the five targeted loci in the different subgroups of patients: GR, PR and the population combining different events such as partial remission, relapse and deaths (event).
© Copyright Policy
Related In: Results  -  Collection

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

fig3: Allelic imbalance (AI) frequencies and percentages of normal (N) status at the five targeted loci in the different subgroups of patients: GR, PR and the population combining different events such as partial remission, relapse and deaths (event).
Mentions: A high level of AI frequency was observed at each locus, except for the microsatellite targeting 7q31. Taking into account heterozygous loci, AI was found in 83% (29 out of 35) for TP53, 71% (27 out of 38) for RB1, 66% (23 out of 35) for D9S171, 34% (11 out of 32) for D7S486 and 58% (26 out of 45) for D5S346 and D5S492 (Table 1). Furthermore, a slightly higher proportion of homozygous loci, than reported in the database, was observed at D7S486 (41 vs 35% for TP53, 30% for RB1, 35% for D9S171 and 17% for 5q21). At least one of the cell cycle genes, p53, Rb or locus 9p21, was altered in 88% biopsies. In order to analyse the data at the locus containing APC, we used two microsatellites flanking this region (D5S346 and D5S492), and considered this locus as informative if it was heterozygous for both markers or if at least one of the two markers was modified, and the second one noninformative. In cases where both microsatellites (D5S346 and D5S492) were informative, results at both sites were always identical, either both AI or both normal. In GR and PR subgroups, AI frequencies for each microsatellite did not show statistical differences (Figure 3Figure 3

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