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犬骨肉瘤中的TP53基因突变

TP53 gene mutations in canine osteosarcoma.

作者信息

Kirpensteijn Jolle, Kik Marja, Teske Erik, Rutteman Gerard R

机构信息

Department of Clinical Sciences of Companion Animals and Pathobiology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.

出版信息

Vet Surg. 2008 Jul;37(5):454-60. doi: 10.1111/j.1532-950X.2008.00407.x.

Abstract

OBJECTIVE

To investigate mutations of the TP53 gene in canine osteosarcoma (OS).

STUDY DESIGN

Clinical historic cohort study.

ANIMALS

Client-owned dogs.

METHODS

OS (n=59) were screened for mutations of the complete TP53 gene using polymerase chain reaction and the mutation was analyzed by single-strand conformational polymorphism. Clinical outcome of dogs with TP53-mutated OS were compared with dogs with OS without a mutation after complete surgical excision of the primary tumor.

RESULTS

TP53 gene mutations were observed in 24 of 59 (40.7%) OS; 3 mutated OS had 2 mutations. The alterations consisted mainly of point mutations (74%). Dogs with mutated OS had a significantly shorter survival time (ST) after surgery than dogs with normal tumor TP53 gene expression (P=.03). Other significant prognosticators for ST and disease-free interval included elevated serum alkaline phosphatase (P<.01) and tumor grade (P=.01).

CONCLUSION

TP53 genetic mutations are common in canine OS and may have a prognostic value.

CLINICAL RELEVANCE

Mutations of the TP53 gene may influence survival and should be considered when evaluating canine OS.

摘要

目的

研究犬骨肉瘤(OS)中TP53基因的突变情况。

研究设计

临床历史队列研究。

动物

客户拥有的犬只。

方法

使用聚合酶链反应对59例骨肉瘤(OS)进行完整TP53基因的突变筛查,并通过单链构象多态性分析突变情况。在对原发性肿瘤进行完整手术切除后,将TP53基因发生突变的骨肉瘤病犬的临床结局与未发生突变的骨肉瘤病犬进行比较。

结果

59例骨肉瘤(OS)中有24例(40.7%)观察到TP53基因突变;3例突变的骨肉瘤有2处突变。改变主要为点突变(74%)。与肿瘤TP53基因表达正常的犬相比,TP53基因发生突变的骨肉瘤病犬术后存活时间(ST)显著缩短(P = 0.03)。存活时间和无病间期的其他重要预后指标包括血清碱性磷酸酶升高(P < 0.01)和肿瘤分级(P = 0.01)。

结论

TP53基因突变在犬骨肉瘤中常见,可能具有预后价值。

临床意义

TP53基因突变可能影响生存,在评估犬骨肉瘤时应予以考虑。

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