AMELOGENIN DOSAGE COMPENSATION IN CARCINOMA OF COLON, LUNG, LIVER ANDKIDNEY, IS NOT A MARKER OF CLONALITY IN MALES

The analysis of patterns of X-chromosome inactivation is becoming incr easingly utilized as a marker of clonal composition oi tissues from wo men. To date, however, no analogous system has been found for the stud y of clonality in tissue from men. In the current study, the methylati on patterns for portions of the amelogenin genes are tested, which are encoded on both the X- and Y-chromosome (AMGX and AMGY). The polymera se chain reaction (PCR) was used to amplify portions of AMGX and AMGY from genomic DNA of carcinomas of the colon, lung, liver and kidney, a s well as from matched normal somatic tissues. The amplification targe t included Alu I methylation sensitive restriction endonuclease sites as well as a 189 bp sequence which is present in AMGX but is absent in AMGY. Polymerase chain reaction amplification of AMGX and AMGY was su ccessful using genomic DNA from both tumour and normal control tissue in 24 of the 26 cases. Pretreatment of genomic DNA with Alu I blocked amplification of AMGX in all cases from both normal tissue and tumour. This indicates that AMGX and AMGY undergo a non-random pattern of met hylation in both normal tissues and in tumours, precluding their use a s a marker of clonality. Methylation of Alu I sites in AMGY suggests t hat the amelogenin genes undergo dosage compensation, which raises the possibility that the expression of amelogenin is not restricted to th e development of the tooth bud but may also play some other role in va rious tissues of the body. (C) 1998 Academic Press.