Gain of an X chromosome is observed as a secondary, acquired karyotypic alteration in a significant proportion of malignant lymphomas. To determine the potential involvement of X-linked genes in neoplastic development, we have analyzed the inactivation status of the supernumerary X chromosome in lymphomas in both male and female patients. In males, neither methylation of FMR1 nor expression of XIST was detected, demonstrating that the duplicated chromosome was not subject to inactivation. In females, both expressed polymorphisms and polymorphisms associated with methylation differences between the active and inactive X chromosome were analyzed to determine whether the duplicated chromosome was active or inactive. To facilitate this analysis, allele-specific PCR primers were designed for detection of previously described polymorphisms in the IDSX and G6PD genes. The female lymphomas were shown to be clonal in origin, and duplication of either the active (5 cases) or inactive (4 cases) X chromosome was observed. Correlations between clinical status and the inactivation status of the X chromosome involved in the duplication were not observed in our relatively small sample, although 4/4 informative cases with a t(14;18) showed duplication of the active X chromosome. In the course of these studies, we detected hypermethylation of the androgen receptor (AR) locus in an extremely high proportion of both male (7/9) and female (9/10) samples. These results are discussed with respect to whether sex chromosome aneuploidies in tumors are involved in, or simply the result of, the neoplastic process. Genes Chromosomes Cancer 28:246-257, 2000.
Copyright 2000 Wiley-Liss, Inc.