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Statements

Subject Item
n2:RIV%2F00064173%3A_____%2F12%3A00003514%21RIV13-MZ0-00064173
rdf:type
n12:Vysledek skos:Concept
dcterms:description
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 gastro-intestinal 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. 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 gastro-intestinal 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.
dcterms:title
High frequency of complex TP53 mutations in CNS metastases from breast cancer High frequency of complex TP53 mutations in CNS metastases from breast cancer
skos:prefLabel
High frequency of complex TP53 mutations in CNS metastases from breast cancer High frequency of complex TP53 mutations in CNS metastases from breast cancer
skos:notation
RIV/00064173:_____/12:00003514!RIV13-MZ0-00064173
n12:predkladatel
n13:ico%3A00064173
n4:aktivita
n6:S n6:I
n4:aktivity
I, S
n4:cisloPeriodika
2
n4:dodaniDat
n10:2013
n4:domaciTvurceVysledku
n17:1293354
n4:druhVysledku
n9:J
n4:duvernostUdaju
n11:S
n4:entitaPredkladatele
n18:predkladatel
n4:idSjednocenehoVysledku
138925
n4:idVysledku
RIV/00064173:_____/12:00003514
n4:jazykVysledku
n14:eng
n4:klicovaSlova
triple-negative breast cancer; p53; CNS metastasis; breast cancer
n4:klicoveSlovo
n8:p53 n8:triple-negative%20breast%20cancer n8:CNS%20metastasis n8:breast%20cancer
n4:kodStatuVydavatele
GB - Spojené království Velké Británie a Severního Irska
n4:kontrolniKodProRIV
[DBFB0C4D84F3]
n4:nazevZdroje
British Journal of Cancer
n4:obor
n5:FD
n4:pocetDomacichTvurcuVysledku
1
n4:pocetTvurcuVysledku
14
n4:rokUplatneniVysledku
n10:2012
n4:svazekPeriodika
106
n4:tvurceVysledku
Gojiš, Ondřej
n4:wos
000299321100023
s:issn
0007-0920
s:numberOfPages
8
n15:doi
10.1038/bjc.2011.464