Oligodendroglial tumors: Refinement of candidate regions on chromosome arm 1p and correlation of 1p/19q status with survival
Oligodendroglial tumors: Refinement of candidate regions on chromosome arm 1p and correlation of 1p/19q status with survival
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DOI：
10.1111/j.1750-3639.2004.tb00044.x
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发表时间：
2004-04-01
期刊：
影响因子：
6.4
通讯作者：
Reifenberger, G
中科院分区：
文献类型：
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作者：
Felsberg, J;Erkwoh, A;Reifenberger, G
染色体臂1 p和19 q上的杂合性丢失（洛）在少突胶质细胞瘤中很常见，并且与间变性少突胶质细胞瘤的化疗敏感性和良好预后相关。1 p和19 q上的少突胶质细胞瘤相关肿瘤抑制基因尚不清楚。为了缩小1 p上的候选区域，我们研究了89例患者的少突胶质细胞肿瘤1 p上多达30个多态性位点的洛合性缺失。此外，所有肿瘤均在19 q上的7个位点进行了洛缺失研究。24例少突胶质细胞瘤中20例（83%）、24例间变性少突胶质细胞瘤中15例（63%）、18例少突星形细胞瘤中10例（56%）和23例间变性少突星形细胞瘤中12例（52%）检测到1 p和19 q的联合洛缺失。5个肿瘤显示1 p部分缺失，这允许分别在D152633远端的1p36.31-pter、D1 S489和D1 S2642之间的1p36.22-p36.31以及D1 S2743和D1 S482之间的1p34.2-p36.1定义3个不同的候选区域。在19 q上未检测到部分缺失。p和19 q的联合洛缺失与疾病进展时间（TTP）延长、总生存期（OS）延长和5年生存率升高相关。根据1 p和19 q上是否存在联合洛缺失，接受辅助放疗和/或化疗的间变性少突胶质细胞肿瘤患者的中位TTP分别为86个月和39个月，中位OS分别为91个月和46个月，5年生存率分别为80%和36%。同样，1 p和19 q的洛缺失与低级别少突胶质细胞肿瘤患者的生存期延长相关（TTP：57个月vs 47个月; OS：172个月vs 105个月; 5年生存率：92% vs 70%）。因此，我们的研究结果细化了1 p上的少突胶质细胞瘤抑制基因的位置，并支持1 p和19 q上的洛缺失作为一个有利的预后标记的意义。
Loss of heterozygosity (LOH) on the chromosome arms 1p and 19q is frequent in oligodendroglial tumors and has been correlated with chemosensitivity and good prognosis in anaplastic oligodendrogliomas. The oligodendroglioma-associated tumor suppressor genes on 1p and 19q are as yet unknown. To narrow down candidate regions on 1p, we investigated oligodendroglial tumors from 89 patients for LOH at up to 30 polymorphic loci on 1p. In addition, all tumors were studied for LOH at 7 loci on 19q. Combined LOH on 1p and 19q was detected in 20 (83%) of 24 oligodendrogliomas, 15 (63%) of 24 anaplastic oligodendrogliomas, 10 (56%) of 18 oligoastrocytomas, and 12 (52%) of 23 anaplastic oligoastrocytomas. Five tumors demonstrated partial deletions on 1p, which allowed to define 3 distinct candidate regions at 1p36.31-pter distal to D152633, 1p36.22-p36.31 between D1S489 and D1S2642, and 1p34.2-p36.1 between D1S2743 and D1S482, respectively. No partial deletions were detected on 19q. Combined LOH on p and 19q was associated with prolonged time to progression (TTP), longer overall survival (OS), and a higher 5-year survival rate. Depending on the presence or absence of combined LOH on 1p and 19q, patients with anaplastic oligodendroglial tumors treated with adjuvant radio- and/or chemotherapy showed a median TTP of 86 months versus 39 months, a median OS of 91 months versus 46 months, and a 5-year survival rate of 80% versus 36%, respectively. Similarly, LOH on 1p and 19q was associated with longer survival in patients with low-grade oligodendroglial tumors (TTP: 57 months versus 47 months; OS: 172 months versus 105 months; 5-year survival rate: 92% versus 70%). Thus, our results refine the location of putative oligodendroglioma suppressor genes on 1p and support the significance of LOH on 1p and 19q as a favorable prognostic marker.