HOX gene methylation status analysis in patients with hereditary breast cancer.
Cancer development is related not only to genetic alterations but also to aberrant epigenetic changes that could lead to heritable gene patterns critical for neoplastic initiation and progression. Knowledge of epigenetic regulation in cancer cells is useful for both the understanding of carcinogenesis and for the possibility of using epigenetic drugs. HOX genes deregulation have a crucial role in oncogenesis process and tumor suppression. In this report, the methylation of HOXA1, HOXA9, HOXA10, HOXB13, HNF1B, OTX1, TLX1 genes have been analyzed in patients with hereditary breast cancer. This is the first study analyzing BRCA mutational status of patients with respect to methylation of HOX genes. HOXA10 has been found to be methylated in all patients analyzed but never in healthy subjects. With respect to clinical pathological information, hypermethylation of all studied genes, with the exception of OTX1, was significantly associated with absence of HER2 neu expression (P<0.05). Moreover, hypermethylation of HOXB13, HOXA10 and HOXA1 was associated with a high proliferation index (Mib1≥10%, P<0.05) and hypermethylation of HOXB13 and HOXA10 also with high expression of estrogen and progesterone receptors. These preliminary data suggest a possible involvement of HOX genes in familial breast cancer as marker helpful to identify high-risk patients.
National Cancer Research Centre, Istituto Tumori Giovanni Paolo II, Bari, Italy.
Brunella
B
Pilato
Rosamaria
R
Pinto
Simona
S
De Summa
Rossana
R
Lambo
Angelo
A
Paradiso
Stefania
S
Tommasi
D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism; D024682:BRCA2 Protein / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005801:Genes, Homeobox / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism
D019313:BRCA1 Protein; D024682:BRCA2 Protein; D018719:Erb-b2 Receptor Tyrosine Kinases; C492913:BRCA1 protein, human; C551750:BRCA2 protein, human; C508053:ERBB2 protein, human