Promoter methylation of the PTEN gene is a common molecular change in breast cancer.
About 25-50% of women with Cowden disease, a syndrome associated with germ-line mutations of the PTEN gene (at 10q23), develop breast cancer (BC), but PTEN mutations have been found in only 5% of sporadic BCs. However, 29-48% of BCs display loss of heterozygosity in 10q23, and about 40% of BCs show a decrease or absence of PTEN protein levels at the time of diagnosis. Promoter hypermethylation has been identified as an alternative mechanism of tumor-suppressor gene inactivation, but its importance in PTEN silencing in sporadic BC is unknown. We investigated PTEN promoter hypermethylation in 90 sporadic BCs and its correlations with 11 molecular and pathologic parameters, including mRNA levels of PTEN. The study, a methylation-specific PCR assay, was carried out with methylated specific primers designed in a region with scarce homology with the psiPTEN pseudogene. Expression was analyzed by real-time PCR. We found that the PTEN promoter was hypermethylated in 43 BCs (48%). PTEN hypermethylation was associated with ERBB2 overexpression, larger size, and higher histologic grade (P=0.012, 0.03, and 0.009, respectively). We concluded that PTEN promoter hypermethylation is a common event in sporadic BC, correlating with other well-established prognostic factors of this malignancy. Additionally, PTEN mRNA expression was lower in tumors with aberrant methylation.
Department of Medical Oncology, Hospital Universitario Puerta de Hierro, Madrid, Spain.
Jose M
JM
García
Javier
J
Silva
Cristina
C
Peña
Vanesa
V
Garcia
Rufo
R
Rodríguez
Miguel A
MA
Cruz
Blanca
B
Cantos
Mariano
M
Provencio
Pilar
P
España
Felix
F
Bonilla
D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D019175:DNA Methylation; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D008875:Middle Aged; D008969:Molecular Sequence Data; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D017931:DNA Primers; D004273:DNA, Neoplasm; D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human