Spectrum of p53 mutations in biopsies from breast cancer patients selected for preoperative chemotherapy analysed by the functional yeast assay to predict therapeutic response

Deissler, Helmut; Kafka, Ariane; Schuster, Eva; Sauer, Georg; Zeillinger, Robert

doi:10.3892/or.11.6.1281

Cited by 16 publications

(16 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Determination of gene mutation TP53 mutation was determined by a modified p53 functional yeast assay [23,24], and Sanger sequencing. In addition, ddPCR systems for each unique TP53 mutation were established to determine the percentage of the TP53 mutant cells in cell culture (Table 1).…”

Section: Dna and Rna Isolationmentioning

confidence: 99%

Molecular characterization of 7 new established cell lines from high grade serous ovarian cancer

et al. 2015

Self Cite

View full text Add to dashboard Cite

Cancer cell lines are good in vitro models to study molecular mechanisms underlying chemoresistance and cancer recurrence. Recent works have demonstrated that most of the available ovarian cancer cell lines are most unlikely high grade serous (HGSOC), the major type of epithelial ovarian cancer. We aimed at establishing well characterized HGSOC cell lines, which can be used as optimal models for ovarian cancer research. We successfully established seven cell lines from HGSOC and provided the major genomic alterations and the transcriptomic landscapes of them. They exhibited different gene expression patterns in the key pathways involved in cancer resistance. Each cell line harbored a unique TP53 mutation as their corresponding tumors and expressed cytokeratins 8/18/19 and EpCAM. Two matched lines were established from the same patient, one at diagnosis and being sensitive to carboplatin and the other during chemotherapy and being resistant. Two cell lines presented respective BRCA1 and BRCA2 mutations. To conclude, we have established seven cell lines and well characterized them at genomic and transcriptomic levels. They are optimal models to investigate the molecular mechanisms underlying the progression, chemo resistance and recurrence of HGSOC.

show abstract

Section: Dna and Rna Isolationmentioning

confidence: 99%

Molecular characterization of 7 new established cell lines from high grade serous ovarian cancer

et al. 2015

Self Cite

View full text Add to dashboard Cite

show abstract

“…[18][19][20][21][22][23] Considering primary (pre-surgical) treatment of breast cancer, TP53 mutations have been associated with anthracycline and mitomycin resistance, 12,[24][25][26] but not with taxane resistance; 26,27 similarly, one study evaluating efficacy of taxanes in the adjuvant setting 28 and two studies evaluating anthracyclines and taxanes administered in concert, or sequentially, found no effect of TP53 mutation status on response. 29,30 Yet, there is evidence at variance. Thus, de The and colleagues 31 found TP53 mutations to predict improved response to chemotherapy in breast cancer; this effect, however, was observed among patients receiving cyclophosphamide at high doses in concert with anthracyclines.…”

Section: Tp53mentioning

confidence: 99%

Mapping genetic alterations causing chemoresistance in cancer: identifying the roads by tracking the drivers

Lønning

Knappskog

2013

Oncogene

View full text Add to dashboard Cite

Although new agents are implemented to cancer therapy, we lack fundamental understandings of the mechanisms of chemoresistance, the main obstacle to cure in cancer. Here we review clinical evidence linking molecular defects to drug resistance across different tumour forms and discuss contemporary experimental evidence exploring these mechanisms. Although evidence, in general, is sparse and fragmentary, merging knowledge links drug resistance, and also sensitivity, to defects in functional pathways having a key role in cell growth arrest or death and DNA repair. As these pathways may act in concert, there is a need to explore multiple mechanisms in parallel. Taking advantage of massive parallel sequencing and other novel high-throughput technologies and base research on biological hypotheses, we now have the possibility to characterize functional defects related to these key pathways and to design a new generation of studies identifying the mechanisms controlling resistance to different treatment regimens in different tumour forms.

show abstract

“…It is interesting to note that this residue, which is located within the DNA-binding domain of p53 (Cho et al, 1994), has also been found to be mutated in a limited number of cancers (Meyers et al, 1993;Hashimoto et al, 1999;Hayes et al, 1999;Deissler et al, 2004;Leitao et al, 2004). The functional significance of p53K120Ac was demonstrated by experiments where K120 acetylation was abolished in cells, either by direct mutation or by depletion of hMOF (or Tip60).…”

Section: The Hmof-atm Connectionmentioning

confidence: 99%

Males absent on the first (MOF): from flies to humans

2007

View full text Add to dashboard Cite

Histone modifications such as acetylation, methylation and phosphorylation have been implicated in fundamental cellular processes such as epigenetic regulation of gene expression, organization of chromatin structure, chromosome segregation, DNA replication and DNA repair. Males absent on the first (MOF) is responsible for acetylating histone H4 at lysine 16 (H4K16) and is a key component of the MSL complex required for dosage compensation in Drosophila. The human ortholog of MOF (hMOF) has the same substrate specificity and recent purification of the human and Drosophila MOF complexes showed that these complexes were also highly conserved through evolution. Several studies have shown that loss of hMOF in mammalian cells leads to a number of different phenotypes; a G 2 /M cell cycle arrest, nuclear morphological defects, spontaneous chromosomal aberrations, reduced transcription of certain genes and an impaired DNA repair response upon ionizing irradiation. Moreover, hMOF is involved in ATM activation in response to DNA damage and acetylation of p53 by hMOF influences the cell's decision to undergo apoptosis instead of a cell cycle arrest. These data, highlighting hMOF as an important component of many cellular processes, as well as links between hMOF and cancer will be discussed.

show abstract

Spectrum of p53 mutations in biopsies from breast cancer patients selected for preoperative chemotherapy analysed by the functional yeast assay to predict therapeutic response

Cited by 16 publications

References 0 publications

Molecular characterization of 7 new established cell lines from high grade serous ovarian cancer

Molecular characterization of 7 new established cell lines from high grade serous ovarian cancer

Mapping genetic alterations causing chemoresistance in cancer: identifying the roads by tracking the drivers

Males absent on the first (MOF): from flies to humans

Contact Info

Product

Resources

About