Correlation of telomere length shortening with TP53 somatic mutations, polymorphisms and allelic loss in breast tumors and esophageal cancer
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AbstractGenomic instability caused by telomere erosion is an important mechanism of tumorigenesis. p53 plays a key role in cellular senescence and/or apoptosis associated with telomere erosion which positions p53 as a guard against tumorigenesis. The present study was undertaken to investigate the potential interactions between p53 functional mutations, polymorphisms, allelic loss and telomere erosion in 126 breast tumor patients and 68 esophageal cancer patients. Telomere length (TL) was measured by real-time quantitative PCR. Somatic mutations, polymorphisms and allelic loss in the TP53 gene were detected by direct sequencing of both tumor and normal tissue samples. Our results showed that telomeres were significantly shorter in tumors with somatic p53 mutations compared with tumors with wild-type p53 in both breast tumors (P=0.007) and esophageal cancer (P=0.001). Telomeres of patients with minor genotype CC of rs12951053 and GG of rs1042522 were significantly shorter compared to patients with other genotypes of this single nucleotide polymorphism in esophageal cancer tissue. Furthermore, TP53 allelic loss was detected and significantly associated with somatic mutations in both types of tumor tissues. These findings suggest that somatic p53 mutations, rs12951053 genotype CC and rs1042522 genotype GG contribute to erosion of telomeres, and TP53 allelic loss may be one of the representations of chromosomal instability caused by telomere erosion combined with somatic p53 mutations. These results support that the TP53 gene has a strong interaction with TL erosion in tumorigenesis.
All Author(s) ListHao XD, Yang Y, Song X, Zhao XK, Wang LD, He JD, Kong QP, Tang NLS, Zhang YP
Journal nameOncology Reports
Volume Number29
Issue Number1
PublisherSpandidos Publications
Pages226 - 236
LanguagesEnglish-United Kingdom
Keywordsallelic loss; breast tumor; esophageal cancer; telomere erosion; TP53 variations
Web of Science Subject CategoriesOncology; ONCOLOGY

Last updated on 2020-20-10 at 01:09