Secondary radiation-induced bone tumours demonstrate a high degree of genomic instability predictive of a poor prognosis.
Secondary radiation-induced bone tumours demonstrate a high degree of genomic instability predictive of a poor prognosis.
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DOI：
10.2174/138920212802510420
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发表时间：
2012-09
期刊：
影响因子：
2.6
通讯作者：
Rosemann M
中科院分区：
文献类型：
--
作者：
Rümenapp C;Smida J;Gonzalez-Vasconcellos I;Baumhoer D;Malfoy B;Hadj-Hamou NS;Sanli-Bonazzi B;Nathrath M;Atkinson MJ;Rosemann M
继发性骨肿瘤发生在之前的放射治疗领域是一个严重的晚期效应，特别是考虑到儿童恶性肿瘤治疗患者的生存时间增加。一般来说，已知与治疗相关的肿瘤与原发肿瘤相比，表现出更具攻击性的行为和对化疗的有限反应。然而，尚不清楚这种不利的结果是由肿瘤细胞的固有遗传因素还是由患者的一般全身状况引起的。为了阐明这一点，我们分析了一系列有先前辐照史的骨肉瘤，以寻找基因组改变的存在，并将它们与早期在原发性骨肉瘤中发现的改变进行了比较。我们使用Affymetrix 10K2高密度单核苷酸多态性（SNP）阵列分析了7例辐射诱导的骨肉瘤的全基因组杂合性损失（LOH）。此外，我们分析了10q上两个不同位点的拷贝数变化，这些位点最近被发现在原发性骨肉瘤中具有重要的预后意义。所有研究的肿瘤的LOH均为10q21.1, 86%的病例（6/7）显示全基因组LOH评分高于2400，超过24%的基因组受到影响。我们的研究结果表明，在放射诱导的骨肉瘤和预后不良的原发性骨肉瘤中存在类似的遗传改变。我们推测，在这些肿瘤中发现的高度基因组不稳定性导致预后不良，无论起始事件如何。
Secondary bone tumours arising in the field of a preceding radiotherapy are a serious late effect, in particular considering the increasing survival times in patients treated for paediatric malignancies. In general, therapy associated tumours are known to show a more aggressive behaviour and a limited response to chemotherapy compared with their primary counterparts. It is not clear however whether this less favourable outcome is caused by inherent genetic factors of the tumour cells or by a general systemic condition of the patient. To elucidate this we analysed a series of bone sarcomas with a history of prior irradiation for the presence of genomic alterations and compared them with the alterations identified earlier in primary osteosarcomas. We analysed seven radiation induced bone sarcomas for genome-wide losses of heterozygosity (LOH) using Affymetrix 10K2 high-density single nucleotide polymorphism (SNP) arrays. Additionally, copy number changes were analysed at two distinct loci on 10q that were recently found to be of major prognostic significance in primary osteosarcomas. All the investigated tumours showed a LOH at 10q21.1 with 86% of cases (6/7) revealing a total genome-wide LOH score above 2400 and more than 24% of the genome being affected. Our results indicate similar genetic alterations in radiation induced sarcomas of bone and primary osteosarcomas with a poor prognosis. We speculate that the high degree of genomic instability found in these tumours causes the poor prognosis irrespective of the initiating event.
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影响因子：
158.5
作者：
TUCKER, MA;DANGIO, GJ;FRAUMENI, JF
通讯作者：
FRAUMENI, JF
影响因子：
2.2
作者：
SPIESS, H;MAYS, CW
通讯作者：
MAYS, CW
影响因子：
45.3
作者：
Bielack, SS;Kempf-Bielack, B;Winkler, K
通讯作者：
Winkler, K
影响因子：
11.5
作者：
Smida, Jan;Baumhoer, Daniel;Nathrath, Michaela
通讯作者：
Nathrath, Michaela
影响因子：
1.7
作者：
CHMELEVSKY, D;KELLERER, AM;SPIESS, H
通讯作者：
SPIESS, H