[Promoter methylation profile in breast cancer].
BACKGROUND
Genomic DNA methylation, mutations and allelic deletions explain the inactivation of genes involved in cell proliferation and cell cycle control mechanisms.


OBJECTIVE
To analyze the methylation pattern of important genes related to different carcinogenic mechanisms in patients with breast cancer and the relationship with its biological behavior.


METHODS
Seventy fresh-frozen breast cancer samples were selected. The methylation specific PCR (MSP) test was used to analyze promoter methylation status for genes CDKN2A (p16), hMLH1, APC, CDH1 (Cadherin E) and FHIT.


RESULTS
We found methylation in at least one of the genes studied in 88% of cases and in 3 or more genes in 40.5% of cases. The frequencies of promoter hypermethylation of CDKN2A, hMLH1, APC, CDH1 and FHT were 41.4%, 11.4%, 52.9%, 70% and 42.9%, respectively. We found a relationship between CDKN2A methylatlon and better survival (p=0.002). CDH1 methylation and poor histological differentiation (p=0.007), hMLH1 methylation and non-Mapuche ethnicity (p=-0.03), APC methylation and larger tumor size (p<0.05), FHIT methylatton and lack of estrogen rectptor IHC expression (p<0.05).


CONCLUSIONS
The high frequency of promoter methylation in patients with breast cancer confirms its role in breast carcinogenesis. The finding of alterations in the methylation pattern of genes studied and its association with prognostic factors is a helpful tool in the search of new criteria for clinical and therapeutic decision making.
Roa
Juan Carlos
JC
Departamento de Anatomía Patológica, Facultad de Medicina, Universidad de La Frontera, Temuco, Chile. jcroa@ufro.cl
Anabalón
Leonardo
L
Tapia
Oscar
O
Martínez
Javier
J
Araya
Juan Carlos
JC
Villaseca
Miguel
M
Guzmán
Pablo
P
Roa
Iván
I
D017766:Acid Anhydride Hydrolases / Q000235:genetics; D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D015820:Cadherins / Q000235:genetics; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000473:pathology; D002352:Carrier Proteins; D016022:Case-Control Studies; D019175:DNA Methylation; D005260:Female; D005784:Gene Amplification / Q000235:genetics; D017491:Genes, APC; D016147:Genes, Tumor Suppressor; D019942:Genes, p16; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D011401:Promoter Regions, Genetic / Q000235:genetics*; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D048868:Adaptor Proteins, Signal Transducing; D015820:Cadherins; D002352:Carrier Proteins; D000070957:MutL Protein Homolog 1; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000099170:Bis(5'-adenosyl)triphosphatase; C501486:MLH1 protein, human