title: Correlation of telomere length shortening with TP53 somatic mutations,             polymorphisms and allelic loss in breast tumors and esophageal cancer.
abstract: Genomic 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.
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, and Yunnan Laboratory of Molecular Biology of Domestic Animals, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, PR China.
authors.forename: Xiao-Dan
authors.initials: XD
authors.lastname: Hao
authors.forename: Yue
authors.initials: Y
authors.lastname: Yang
authors.forename: Xin
authors.initials: X
authors.lastname: Song
authors.forename: Xue-Ke
authors.initials: XK
authors.lastname: Zhao
authors.forename: Li-Dong
authors.initials: LD
authors.lastname: Wang
authors.forename: Jun-Dong
authors.initials: JD
authors.lastname: He
authors.forename: Qing-Peng
authors.initials: QP
authors.lastname: Kong
authors.forename: Nelson Leung Sang
authors.initials: NL
authors.lastname: Tang
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Zhang
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D042822:Genomic Instability; D006801:Humans; D019656:Loss of Heterozygosity; D009154:Mutation / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D016615:Telomere / Q000235:genetics*; D059506:Telomere Shortening; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53