p53 mutations predict non-small cell lung carcinoma response to radiotherapy

Matsuzoe, Daisuke; Hideshima, Teru; Kimura, Akinori; Inada, Kazuo; Watanabe, Kenshi; Akita, Yuzo; Kawahara, Katsunobu; Shirakusa, Takayuki

doi:10.1016/s0304-3835(98)00292-4

Cited by 25 publications

(13 citation statements)

References 18 publications

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“…However, our data support the idea that there may be combined effects of the TP53 and p21 polymorphisms since there was a clear difference in the occurrence of acute toxicity by BMI for women with TP53 72Pro alleles and p21 Ser/Ser genotype. Matsuzoe et al [34] reported that loss of p53 function decreased radiation sensitivity in non-small cell lung carcinoma, however, no significant difference between the p21 polymorphisms and response to radiation was found. An interaction between p21 Ser31Arg and TP53 Arg72Pro was also not observed for the risk of breast cancer [28].…”

Section: Discussionmentioning

confidence: 98%

Association between TP53 and p21 genetic polymorphisms and acute side effects of radiotherapy in breast cancer patients

Tan

Popanda

Ambrosone

et al. 2005

Breast Cancer Res Treat

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p53 and p21 play an important role in G1/S checkpoint control in response to ionizing radiation. Yet the genetic polymorphisms in these genes have not been investigated with respect to radiation toxicity in patients. We therefore assessed the association between TP53 Arg72Pro, p53PIN3 and p21 Ser31Arg polymorphisms and the risk of acute skin toxicity after radiotherapy in a prospective study of 446 female breast cancer patients (average age 60.3+/-9.0 years) receiving radiotherapy after breast conserving surgery. The p53PIN3 polymorphism was determined by standard PCR, and TP53 Arg72Pro and p21 Ser31Arg polymorphisms using melting point analysis of sequence-specific hybridization probes. The development of acute skin toxicity (moist desquamation) was modelled using Cox proportional hazards, accounting for cumulative biologically effective radiation dose. Overall, the development of acute skin toxicity, which presented in 77 patients, was not significantly associated with the polymorphisms studied. Risks were however differential by body mass index. Compared to non-carriers, TP53 72Pro carriers had a non-significantly decreased risk of acute skin toxicity in normal weight women (hazard ratio 0.46, 95% CI, 0.18-1.18) but not in overweight patients (hazard ratio 1.07, 95% CI, 0.61-1.89) (p(interaction) =0.14). Haplotype analysis for the TP53 polymorphisms suggested that effect modification by TP53 72Pro may differ according to the p53PIN3 allele (p(interaction)=0.06). Furthermore, in TP53 72Pro carriers with p21 Ser/Ser genotype, the occurrence of acute toxicity was reduced in normal weight but not overweight patients. In conclusion, the TP53 72Pro variant may be associated with the development of acute skin toxicity after radiotherapy in patients with normal weight. Large clinical studies are needed to clearly confirm this association.

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Section: Discussionmentioning

confidence: 98%

Association between TP53 and p21 genetic polymorphisms and acute side effects of radiotherapy in breast cancer patients

Tan

Popanda

Ambrosone

et al. 2005

Breast Cancer Res Treat

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“…Mutant p53 provides tumor cells with a selective survival advantage during nonsurgical therapy and thus decrease the sensitivity to chemo-and radiodrugs. 21,22 Functioning as a transcription factor, p53 binds to DNA in a sequence-specific manner and regulates the transcription of the gene responsible for the promotion of apoptosis and the inhibition of angiogenesis, 23 both of which are believed to be critical for the prevention or the inhibition of the development of tumors. This concept is supported by both animal and human data.…”

Section: Discussionmentioning

confidence: 99%

Mutation of p53 in Recurrent Hepatocellular Carcinoma and Its Association with the Expression of ZBP-89

Chen¹,

Merchant²,

Lai³

et al. 2003

The American Journal of Pathology

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“…Moreover, these data are consistent with clinical outcomes. In patients with locally advanced NSCLC treated with radiation therapy alone, mutant TP53 (by directed sequencing of the DNA binding domain of the gene) resulted in a decreased treatment response (48)(49)(50).…”

Section: Discussionmentioning

confidence: 99%

Integrative Radiogenomic Profiling of Squamous Cell Lung Cancer

Abazeed¹,

Adams

Hurov

et al. 2013

International Journal of Radiation Oncology*Biology*Physics

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Radiation therapy is one of the mainstays of anti-cancer treatment, but the relationship between the radiosensitivity of cancer cells and their genomic characteristics is still not well-defined. Here we report the development of a high-throughput platform for measuring radiation survival in vitro and its validation by comparison to conventional clonogenic radiation survival analysis. We combined results from this high-throughput assay with genomic parameters in cell lines from squamous cell lung carcinoma, which is standardly treated by radiation therapy, to identify parameters that predict radiation sensitivity. We showed that activation of NFE2L2, a frequent event in lung squamous cancers, confers radiation resistance. An expression-based, in silico screen nominated inhibitors of PI3K as NFE2L2 antagonists. We showed that the selective PI3K inhibitor, NVP-BKM120, both decreased NRF2 protein levels and sensitized NFE2L2 or KEAP1 mutant cells to radiation. We then combined results from this high-throughput assay with singlesample gene set enrichment analysis (ssGSEA) of gene expression data. The resulting analysis §

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p53 mutations predict non-small cell lung carcinoma response to radiotherapy

Cited by 25 publications

References 18 publications

Association between TP53 and p21 genetic polymorphisms and acute side effects of radiotherapy in breast cancer patients

Association between TP53 and p21 genetic polymorphisms and acute side effects of radiotherapy in breast cancer patients

Mutation of p53 in Recurrent Hepatocellular Carcinoma and Its Association with the Expression of ZBP-89

Integrative Radiogenomic Profiling of Squamous Cell Lung Cancer

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