Involvement of the X chromosome in non-Hodgkin lymphoma

Gain of an X chromosome is observed as a secondary, acquired karyotypic alt eration in a significant proportion of malignant lymphomas. To determine th e potential involvement of X-linked genes in neoplastic development, we hav e analyzed the inactivation status of the supernumerary X chromosome in lym phomas in both male and female patients. In males, neither methylation of F MRI nor expression of XIST was detected, demonstrating that. the duplicated chromosome was not subject to inactivation, in females, both expressed pol ymorphisms and polymorphisms associated with methylation differences betwee n the active and inactive X chromosome were analyzed to determine whether t he duplicated chromosome was active or inactive. To facilitate this analysi s, allele-specific PCR primers were designed for detection of previously de scribed polymorphisms in the IDSX and G6PD genes. The female lymphomas were shown to be clonal in origin, and duplication of either the active (5 case s) or inactive (4 cases) X chromosome was observed. Correlations between cl inical status and the inactivation status of the X chromosome involved in t he 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 chr omosome. In the course of these studies, we detected hypermethylation of th e 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. (C) 2000 Wiley-Liss, Inc.