Age-dependent prognostic effects of genetic alterations in glioblastoma
Age-dependent prognostic effects of genetic alterations in glioblastoma
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DOI：
10.1158/1078-0432.ccr-0841-3
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发表时间：
2004-01-01
影响因子：
11.5
通讯作者：
Louis, DN
中科院分区：
文献类型：
--
作者：
Batchelor, TT;Betensky, RA;Louis, DN
目的：虽然胶质母细胞瘤的遗传改变已得到很好的表征，但有关其预后影响的报道却不一致。 实验设计：在单中心治疗的这一系列连续 140 例胶质母细胞瘤病例中，我们分析了 TP53 突变、CDKN2A/p16 缺失、EGFR 扩增以及染色体 1p、染色体 10q 和染色体 19q 丢失的频率、年龄依赖性和预后影响。 The complete set of genetic alterations was available on 60 of 140 patients.Results: In this cohort of glioblastoma cases, TP53 mutation was significantly associated with patient age. TP53 突变、EGFR 扩增、CDKN2A/p16 改变和 1p 染色体缺失的预后影响取决于患者的年龄。 结论：这是首次观察到 TP53、1p 和 CDKN2A/p16 改变的预后影响取决于患者年龄。这些关于胶质母细胞瘤中年龄和遗传变化相互作用的观察结果表明，胶质母细胞瘤的致瘤途径随患者年龄的变化而变化，未来的分子标记研究应仔细评估这些生物变量的潜在年龄依赖性预后效应。 The inconsistent or negative prognostic effects of molecular markers reported in prior studies of glioblastoma may be because different effects at different ages may have resulted in a cancellation of an overall effect in the entire cohort.
Purpose: Although the genetic alterations in glioblastoma have been well characterized, reports regarding their prognostic effects have been inconsistent.Experimental Design: In this series of 140 consecutive cases of glioblastoma treated at a single center, we analyzed the frequency, age dependency and prognostic effects of TP53 mutation, CDKN2A/p16 deletion, EGFR amplification, as well as loss of chromosome 1p, chromosome 10q, and chromosome 19q. The complete set of genetic alterations was available on 60 of 140 patients.Results: In this cohort of glioblastoma cases, TP53 mutation was significantly associated with patient age. The prognostic effects of TP53 mutation, EGFR amplification, CDKN2A/p16 alterations, and loss of chromosome 1p were dependent on the age of the patient.Conclusions: This is the first observation that the prognostic effects of TP53, 1p, and CDKN2A/p16 alterations are dependent on patient age. These observations concerning the interactions of age and genetic changes in glioblastoma suggest that tumorigenic pathways to glioblastoma vary with the age of the patient and that future molecular marker studies should carefully evaluate the potential age-dependent prognostic effects of these biological variables. The inconsistent or negative prognostic effects of molecular markers reported in prior studies of glioblastoma may be because different effects at different ages may have resulted in a cancellation of an overall effect in the entire cohort.