Intronic deletion affecting a negative regulatory region of TP73 is related to breast and colorectal carcinomas.
The TP73 gene encodes a nuclear protein that has high homology with TP53. TP73 is rarely mutated in human cancer. The presence of a 1-kb regulatory fragment within the first intron of TP73 was recently reported. This fragment exerts silencer activity on TP73 mediated by ZEB. We searched for possible mutations in this negative regulatory region in 45 colorectal and 43 breast cancer patients and in 34 healthy donors. The study was carried out using the SSCP method, and the allelic variants detected were sequenced. The expression of TP73 was analyzed by quantitative RT-PCR, and loss of heterozygosity (LOH) was assessed by microsatellite study. In several samples, we identified an allele variant that corresponds to a deletion of 73 bp in tumor tissues and normal counterparts, localized between -489 and -417 from the ATG start site of exon 2. Among the 88 tumor samples, 35 (40%) showed at least 1 allele with the cited deletion, versus 7 of the 34 (21%) healthy donors (P = 0.045). When we classified the patients according to the number of variations into homozygous or heterozygous groups, the significance was clearer (P = 0.03). No LOH was detected in the heterozygous cases. There was a positive quantitative correlation between the expression of TP73 and the presence of the allelic variant (P = 0.029). These data suggest that this allelic variant is common in breast and colorectal cancers and that it could alter the expression of the TP73 gene with an additive effect.
Peña
Cristina
C
Department of Medical Oncology, Hospital Universitario Puerta de Hierro, Madrid, Spain. felixbv@stnet.es
Garcia
Jose M
JM
Dominguez
Gemma
G
Silva
Javier
J
Garcia
Vanesa
V
Carcereny
Enric
E
Vargas
Javier
J
Provencio
Mariano
M
España
Pilar
P
Bonilla
Felix
F
D001483:Base Sequence / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D004247:DNA / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D006801:Humans; D007438:Introns / Q000235:genetics*; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D010750:Phosphoproteins; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D004247:DNA