Changes in allelic imbalances in locally advanced breast cancers after chemotherapy
| Autor: | M Varna, H Soliman, J-P Feugeas, E Turpin, D Chapelin, L Legrès, L-F Plassa, A de Roquancourt, M Espié, J-L Misset, A Janin, H de Thé, P Bertheau |
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| Rok vydání: | 2007 |
| Předmět: |
Adult
Cancer Research Pathology medicine.medical_specialty Cyclophosphamide Tumour heterogeneity medicine.medical_treatment Breast Neoplasms Biology Allelic Imbalance chemotherapy Somatic evolution in cancer Polymerase Chain Reaction Loss of heterozygosity Breast cancer breast cancer Antineoplastic Combined Chemotherapy Protocols medicine Humans TP53 Aged Epirubicin Aged 80 and over Chemotherapy Lasers Genetics and Genomics Middle Aged medicine.disease Genes p53 Oncology Mutation Cancer research Female loss of heterozygosity Microdissection medicine.drug |
| Zdroj: | British Journal of Cancer |
| ISSN: | 0007-0920 |
| Popis: | In advanced breast cancers, TP53 mutation is highly predictive of complete response to high-dose epirubicin/cyclophosphamide chemotherapy. In these tumours with an altered control of genomic stability, accumulation of chemotherapy-induced genetic alterations may contribute to cell death and account for complete response. To explore the effects of chemotherapy on stability of the tumour genome, allelic profiles were obtained from microdissected tumour samples before and after chemotherapy in 29 unresponsive breast cancers (9 with TP53 mutation). Ninety-four per cent allelic profiles remained unchanged after treatment. Interestingly, 11 profiles (6%) showed important changes after treatment; allelic imbalances significantly increased (four cases) or decreased (seven cases) after chemotherapy in three distinct experiments, two of which using laser microdissected tumour cells. These genetic changes were not linked to the TP53 status, but one tumour showed complete disappearance of TP53-mutated cells in the residual tumour after treatment. Altogether, these observations carry important implications for the clonal evolution of breast cancers treated with DNA-damaging agents, as they point both to the importance of tumour heterogeneity and chemotherapy-driven selection of subclones. |
| Databáze: | OpenAIRE |
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