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Aberrant hypermethylation of Xq12 in lymphoma Quint, Désirée


It has been well established that abnormal CpG island promoter methylation in cancer is associated with the epigenetic silencing of tumour suppressor genes, genes that when inactivated predispose a cell to malignancy. Such aberrant methylation was seen for the androgen receptor (AR) located on the X chromosome in 84% of follicular lymphoma patient samples. Methylation has been shown to spread several megabases from its origin and this has led us to hypothesize that a candidate tumour suppressor gene is located in the vicinity ofthe AR. AR and the nearby oligophrenin (OPHNl) gene are both considered to be poor tumour suppressor gene candidates since deletions of these genes exist and they do not result in lymphoma. In addition, OPHNI is mainly expressed in brain tissues. In order to identify candidate genes, the extent of the abnormal CpG island methylation within the region surrounding the AR was first established in two different lymphoma cell lines (SUDHL3, DoHH2). A region of approximately 8 Mb was examined which led to the focus on a 1.5 Mb highly methylated sub-region located downstream of the AR. The methylation status of CpG islands within this sub- region was examined in three additional lymphoma cell lines (HBL-2, JVM-2 and 2138) as well as in patient samples. STARD8, a GTPase-activating protein, is located within this region and is abnormally silenced in at least two of the lymphoma cell lines making it a possible candidate.

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