Frequency of the TP53 R337H variant in sporadic breast cancer and its impact on genomic instability
| العنوان: | Frequency of the TP53 R337H variant in sporadic breast cancer and its impact on genomic instability |
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| المؤلفون: | Rubens Silveira de Lima, Carolina Prando, Stefanne Bortoletto, Iglenir J. Cavalli, Ana Paula Martins Sebastião, Cicero Urban, Emerson Wander Silva Soares, Heloisa Komechen, Bonald C. Figueiredo, Aline S. Fonseca, Ariana Centa, Carolina Mathias, Enilze M. Ribeiro, Luciane R. Cavalli |
| المصدر: | Scientific Reports, Vol 10, Iss 1, Pp 1-12 (2020) Scientific Reports |
| بيانات النشر: | Nature Publishing Group, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Genome instability, Family Cancer History, Gene Dosage, lcsh:Medicine, Breast Neoplasms, Biology, Article, Genomic Instability, Germline, Breast cancer, Gene Frequency, Genotype, Cancer genomics, medicine, Humans, Copy-number variation, Codon, lcsh:Science, Cancer genetics, Genotyping, Allele frequency, Germ-Line Mutation, Aged, Multidisciplinary, lcsh:R, Age Factors, Exons, Middle Aged, medicine.disease, Survival Rate, Cancer research, Female, lcsh:Q, Tumor Suppressor Protein p53, Brazil |
| الوصف: | The R337H is a TP53 germline pathogenic variant that has been associated with several types of cancers, including breast cancer. Our main objective was to determine the frequency of the R337H variant in sporadic breast cancer patients from Paraná state, South Brazil, its association with prognosis and its impact in genomic instability. The genotyping of 805 breast cancer tissues revealed a genotypic and allelic frequency of the R337H variant of 2.36% and 1.18%, respectively. In these R337H+ cases a lower mean age at diagnosis was observed when compared to the R337H-cases. Array-CGH analysis showed that R337H+ patients presented a higher number of copy number alterations (CNAs), compared to the R337H−. These CNAs affected genes and miRNAs that regulate critical cancer signaling pathways; a number of these genes were associated with survival after querying the KMplot database. Furthermore, homozygous (R337H+/R337H+) fibroblasts presented increased levels of copy number variants when compared to heterozygous or R337H− cells. In conclusion, the R337H variant may contribute to 2.36% of the breast cancer cases without family cancer history in Paraná. Among other mechanisms, R337H increases the level of genomic instability, as evidenced by a higher number of CNAs in the R337H+ cases compared to the R337H−. |
| اللغة: | English |
| تدمد: | 2045-2322 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a9b8b0e4b892fee2f545c09e1d6acefb http://link.springer.com/article/10.1038/s41598-020-73282-y |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....a9b8b0e4b892fee2f545c09e1d6acefb |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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