Limits...
Mutations in Rb1 pathway-related genes are associated with poor prognosis in anaplastic astrocytomas.

Bäcklund LM, Nilsson BR, Liu L, Ichimura K, Collins VP - Br. J. Cancer (2005)

Bottom Line: Since survival for patients with AA varies markedly and there are no known useful prognostic or therapy response indicators, the primary purpose of this study was to examine whether knowledge of the known genetic abnormalities found in AA had any clinical value.This association was consistent in multivariate analysis, including adjustment for age (P=0.013).The findings suggest that analysis of the genes coding for Rb1 pathway components provides additional prognostic information in AA patients receiving conventional therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden. Magnus.Backlund@onkpat.ki.se

ABSTRACT
Anaplastic astrocytoma (AA, WHO grade III) is, second to Glioblastoma, the most common and most malignant type of adult CNS tumour. Since survival for patients with AA varies markedly and there are no known useful prognostic or therapy response indicators, the primary purpose of this study was to examine whether knowledge of the known genetic abnormalities found in AA had any clinical value. The survival data on 37 carefully sampled AA was correlated with the results of a detailed analysis of the status of nine genes known to be involved in the development of astrocytic tumours. These included three genes coding for proteins in the p53 pathway (TP53, p14(ARF)and MDM2), four in the Rb1 pathway (CDKN2A, CDKN2B, RB1 and CDK4) and PTEN and EGFR. We found that loss of both wild-type copies of any of the three tumour suppressor genes CDKN2A, CDKN2B and RB1 or gene amplification of CDK4, disrupting the Rb1 pathway, were associated with shorter survival (P=0.009). This association was consistent in multivariate analysis, including adjustment for age (P=0.013). The findings suggest that analysis of the genes coding for Rb1 pathway components provides additional prognostic information in AA patients receiving conventional therapy.

Show MeSH

Related in: MedlinePlus

Survival curves for cases with loss of both wild-type alleles of any TSG coding for a component of the Rb1 pathway (CDKN2A, CDKN2B, RB1) or amplification of CDK4, that is, Rb1 pathway classified as ‘abnormal' (n=8; median survival 1.4 years) and cases coded as ‘normal' (n=29; median survival 5.8 years), respectively. Univariate analysis: P=0.009.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2361485&req=5

fig3: Survival curves for cases with loss of both wild-type alleles of any TSG coding for a component of the Rb1 pathway (CDKN2A, CDKN2B, RB1) or amplification of CDK4, that is, Rb1 pathway classified as ‘abnormal' (n=8; median survival 1.4 years) and cases coded as ‘normal' (n=29; median survival 5.8 years), respectively. Univariate analysis: P=0.009.

Mentions: As presented in Table 3, the only single genetic aberration showing a significant negative association with survival was CDK4 amplification. The statistical significance was borderline in univariate analysis (P=0.058) but significant in multivariate analysis adjusting for age and whether the tumour was ‘primary' or ‘recurrent' / ‘progressed' (P=0.019). Disruption of the Rb1 pathway was negatively associated with survival in univariate (P=0.009) as well as in multivariate analysis (P=0.013). The survival curves for the Rb1 pathway groups ‘normal' and ‘abnormal' are shown in Figure 3.


Mutations in Rb1 pathway-related genes are associated with poor prognosis in anaplastic astrocytomas.

Bäcklund LM, Nilsson BR, Liu L, Ichimura K, Collins VP - Br. J. Cancer (2005)

Survival curves for cases with loss of both wild-type alleles of any TSG coding for a component of the Rb1 pathway (CDKN2A, CDKN2B, RB1) or amplification of CDK4, that is, Rb1 pathway classified as ‘abnormal' (n=8; median survival 1.4 years) and cases coded as ‘normal' (n=29; median survival 5.8 years), respectively. Univariate analysis: P=0.009.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2361485&req=5

fig3: Survival curves for cases with loss of both wild-type alleles of any TSG coding for a component of the Rb1 pathway (CDKN2A, CDKN2B, RB1) or amplification of CDK4, that is, Rb1 pathway classified as ‘abnormal' (n=8; median survival 1.4 years) and cases coded as ‘normal' (n=29; median survival 5.8 years), respectively. Univariate analysis: P=0.009.
Mentions: As presented in Table 3, the only single genetic aberration showing a significant negative association with survival was CDK4 amplification. The statistical significance was borderline in univariate analysis (P=0.058) but significant in multivariate analysis adjusting for age and whether the tumour was ‘primary' or ‘recurrent' / ‘progressed' (P=0.019). Disruption of the Rb1 pathway was negatively associated with survival in univariate (P=0.009) as well as in multivariate analysis (P=0.013). The survival curves for the Rb1 pathway groups ‘normal' and ‘abnormal' are shown in Figure 3.

Bottom Line: Since survival for patients with AA varies markedly and there are no known useful prognostic or therapy response indicators, the primary purpose of this study was to examine whether knowledge of the known genetic abnormalities found in AA had any clinical value.This association was consistent in multivariate analysis, including adjustment for age (P=0.013).The findings suggest that analysis of the genes coding for Rb1 pathway components provides additional prognostic information in AA patients receiving conventional therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden. Magnus.Backlund@onkpat.ki.se

ABSTRACT
Anaplastic astrocytoma (AA, WHO grade III) is, second to Glioblastoma, the most common and most malignant type of adult CNS tumour. Since survival for patients with AA varies markedly and there are no known useful prognostic or therapy response indicators, the primary purpose of this study was to examine whether knowledge of the known genetic abnormalities found in AA had any clinical value. The survival data on 37 carefully sampled AA was correlated with the results of a detailed analysis of the status of nine genes known to be involved in the development of astrocytic tumours. These included three genes coding for proteins in the p53 pathway (TP53, p14(ARF)and MDM2), four in the Rb1 pathway (CDKN2A, CDKN2B, RB1 and CDK4) and PTEN and EGFR. We found that loss of both wild-type copies of any of the three tumour suppressor genes CDKN2A, CDKN2B and RB1 or gene amplification of CDK4, disrupting the Rb1 pathway, were associated with shorter survival (P=0.009). This association was consistent in multivariate analysis, including adjustment for age (P=0.013). The findings suggest that analysis of the genes coding for Rb1 pathway components provides additional prognostic information in AA patients receiving conventional therapy.

Show MeSH
Related in: MedlinePlus