High frequency of complex TP53 mutations in CNS metastases from breast cancer

被引：34

作者：

Lo Nigro, C. ^{[2
]}

Vivenza, D. ^{[2
]}

Monteverde, M. ^{[2
]}

Lattanzio, L. ^{[2
]}

Gojis, O. ^{[3
]}

Garrone, O.

Comino, A. ^{[4
]}

Merlano, M.

Quinlan, P. R. ^{[1
]}

Syed, N. ^{[5
]}

Purdie, C. A. ^{[1
]}

Thompson, A. ^{[1
]}

Palmieri, C. ^{[3
]}

Crook, T. ^{[1
]}

机构：

[1] Univ Dundee, Ninewells Hosp, Dundee Canc Ctr, Dundee DD1 9SY, Scotland

[2] S Croce Gen Hosp, Dept Oncol, Lab Canc Genet & Translat Oncol, Cuneo, Italy

[3] Univ London Imperial Coll Sci Technol & Med, Div Canc, Canc Res UK Labs, London W12 0NN, England

[4] S Croce Gen Hosp, Dept Pathol, Cuneo, Italy

[5] Univ London Imperial Coll Sci Technol & Med, Charing Cross Hosp, Ctr Neurosci, Fac Med,John Fulcher Neuro Oncol Lab, London W6 8RF, England

来源：

BRITISH JOURNAL OF CANCER | 2012年 / 106卷 / 02期

关键词：

breast cancer; CNS metastasis; p53; triple-negative breast cancer; P53; MUTATIONS; TUMORS; PROGNOSIS; GENES; BRAIN;

D O I：

10.1038/bjc.2011.464

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

BACKGROUND: Brain metastasis from breast cancer is usually associated with a poor prognosis and early death. Alteration of p53 may contribute to malignant progression by abrogation of apoptosis induced by oncogene activation and by acquisition of gain-of-function properties, which promote tumour aggression. Mutation in TP53 occurs at high frequency in carcinomas of the lung and gastrointestinal tract, but is much less frequent, at 25%, in primary breast cancer. The frequency of TP53 alteration in the central nervous system (CNS) metastatic breast cancer is not known. METHODS: In all, 23 cases of histologically confirmed CNS metastatic breast cancer were identified and the coding sequence of TP53 determined. TP53 was also sequenced in two control series of primary breast carcinomas from independent clinical centres. RESULTS: We demonstrate a strikingly high frequency of TP53 mutation in the CNS metastatic lesions with an over-representation of complex mutations (non-sense/deletions/insertions). Complex mutations occur in metastatic lesions in both triple-negative breast cancer and hormone receptor/HER2-positive cases. Analysis of paired primary carcinomas and brain metastatic lesions revealed evidence for both clonal selection and generation of new mutations (missense and complex) in progression from a primary breast carcinoma to brain metastasis. CONCLUSION: Mutation in TP53 is the most common genetic alteration reported during metastasis to the brain in breast cancer. British Journal of Cancer (2012) 106, 397-404. doi:10.1038/bjc.2011.464 www.bjcancer.com Published online 20 December 2011 (C) 2012 Cancer Research UK

引用

页码：397 / 404

页数：8

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