METHYLATION OF LAMININ-5 ENCODING GENE SUBUNITS IN NORMAL AND BREAST CANCER TISSUES
studied by a single group of researchers (U. G. Sathyanarayana et al., 2003-2004) only. They demonstrated aberrant methylation of these genes in 5 to 40% of breast cancer cases. While methylation of the same loci in DNA from normal lymphocytes, buccal epithelial cells and nonmalignant breast tissue cells was observed in 0 to 7% of cases. Significant associations were found between the aberrant methylation, mRNA expression and clinicomorphological features of the tumors. This study was not repeated by other authors and the results were therefore neither confirmed nor refuted. Nevertheless, the concept of aberrant methylation of LAMA3, LAMB3 and LAMC2 as a principal feature of laminin-5 molecular pathology in cancer became commonly adopted owing to multiple recent reviews. Methyl-sensitive polymerase reaction used in our study detected promoter methylation in LAMA3, LAMB3 and LAMC2 in 96 to 100% of breast cancer specimens, adjacent normal breast tissue and breast sections. Promotor methylation of LAMA3, LAMB3 and LAMC2 was also discovered in all buccal epithelium and blood specimens. Our findings as confirmed by sequencing of bisulfate-converted DNA suggest that the promoter methylation of laminin-5 encoding genes should not be used as a diagnostic marker and that the concept of molecular pathology mechanisms of this laminin type in cancer should be revised.