A role for the p53 pathway in the pathology of meningiomas with NF2 loss.
A role for the p53 pathway in the pathology of meningiomas with NF2 loss.
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DOI：
10.1007/s11060-008-9721-3
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发表时间：
2009-02
影响因子：
3.9
通讯作者：
Nunes, Fabio P.
中科院分区：
文献类型：
--
作者：
Chang, ZeNan;Guo, Chin-Lin;Ahronowitz, Iris;Stemmer-Rachamimov, Anat O.;MacCollin, Mia;Nunes, Fabio P.
在40-65%的散发性脑膜瘤中，神经纤维瘤病2位点（NF 2）通过突变和杂合性缺失（洛）而失活，而p53肿瘤抑制途径在脑膜瘤发生和发展中的作用仍不清楚。本研究的目的是确定p53密码子72脯氨酸-脯氨酸多态性是否与散发性脑膜瘤的发生或进展相关，该多态性与其他肿瘤的癌症发展和癌症患者的生存相关。我们调查了92例散发性脑膜瘤的Pro72发生率，并分析了其与组织学分级（WHO分类）和NF 2洛（使用22 q上的多态性微卫星标记确定）的相关性。未发现Pro72等位基因在队列中被选择。然而，在NF 2洛缺失并携带Pro 72的脑膜瘤亚组中，50.0%的脑膜瘤为高级别肿瘤（WHO II级和III级），而无NF 2洛缺失的脑膜瘤仅为14.3%（OR = 6.0，CI = 1.56-23.11，P = 0.012）。只有在考虑脑膜瘤伴或不伴NF 2洛缺失的亚组时才出现显著相关性，这表明在分析研究队列时不包括NF 2状态可能解释了文献中所有脑膜瘤分组的变异性。我们的数据表明p53通路在NF 2失活的脑膜瘤进展中的作用，并强调了在未来的脑膜瘤和p53通路研究中考虑NF 2洛的重要性。
The neurofibromatosis 2 locus (NF2) is inactivated through mutation and loss of heterozygosity (LOH) in 40–65% of all sporadic meningiomas, while the role of the p53 tumor suppression pathway in meningioma initiation and progression is still unclear. This study aims to determine if a p53 codon 72 arginine-to-proline polymorphism, found to be correlated with cancer development and cancer patient survival in other tumors, is associated with sporadic meningioma initiation or progression. We investigated Pro72 incidence in a cohort of 92 sporadic meningiomas and analyzed its association with histological grade (WHO classification) and with NF2 LOH (determined using polymorphic microsatellite markers on 22q). The Pro72 allele was not found to be selected for in the cohort. However, in the subgroup of meningiomas with NF2 LOH and carrying Pro72, 50.0% had high grade tumors (WHO grades II and III) compared to only 14.3% of those without NF2 LOH (OR = 6.0, CI = 1.56–23.11, P = 0.012). The significant association occurred only when considering subgroups of meningiomas with or without NF2 LOH, suggesting that not including NF2 status when analyzing study cohorts may explain the variability seen in the literature where all meningiomas were grouped together. Our data suggests a role for the p53 pathway in the progression of meningiomas in which NF2 is inactivated, and highlights the importance of accounting for NF2 LOH in future studies of meningiomas and the p53 pathway.
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影响因子：
30.8
作者：
Dumont, P;Leu, JIJ;Murphy, M
通讯作者：
Murphy, M
影响因子：
3.9
作者：
Korhonen, Katariina;Salminen, Tiina;Haapasalo, Hannu
通讯作者：
Haapasalo, Hannu
影响因子：
64.8
作者：
Laurie, Nikia A.;Donovan, Stacy L.;Dyer, Michael A.
通讯作者：
Dyer, Michael A.
影响因子：
3.9
作者：
Al-Khalaf, Huda H.;Lach, Boleslaw;Aboussekhra, Abdelilah
通讯作者：
Aboussekhra, Abdelilah
影响因子：
2.1
作者：
Biros, E;Kalina, I;Sulla, I
通讯作者：
Sulla, I