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Allelic Imbalance Mapped to 6q14.1 Is Associated With Loss of Expression of 5-HT Receptor 1B in Non-Hodgkin Lymphomas

Previous studies on lymphomas suggested that the long arm of chromosome 6 harbors 1 or more tumor suppressor genes. This study analyzed the status of 25 microsatellite markers in 39 cases, including 9 nodal and 30 extranodal, of non-Hodgkin lymphomas. Thirty of the 39 cases (77%) showed abnormality in at least 1 of the markers. Of the 655 informative results, 135 (20%) were abnormal. These included 5 homozygous deletions, 91 allelic imbalances (AI), and 38 microsatellite instability. The 2 commonest regions of abnormality were mapped to 6q14.1 and 6q27. There was no significant difference in the frequency of these regional losses between nodal and extranodal lymphomas, B-or T-cell lineage, and association with Epstein-Barr virus. The first common deletion region at 6q14.1 is flanked by the HTR1B (5-hydroxytryptamine receptor 1B) gene proximally and a novel unknown gene. AI in the region was found associated with loss of expression HTR1B by RT-PCR. The deletion region at 6q27 was narrowed to approximately 3Mb and maximal at marker D6S386. This locus includes the recently identified SMOC2 (secreted modular calcium-binding protein 2), AF6, and DLL1 (human delta-like 1 protein) genes. RT-PCR analyses of AF6 and DLL1 expression showed poor correlation with the AI results.