Familial Occurrence of Thymoma and Autoimmune Diseases with the Constitutional Translocation t(14;20)(q24.1;p12.3)

Thymomas are low-grade epithelial cancers of the thymus whose prevalence varies between 0.1/100,000 and 0.4/100,000. Familial occurrence of thymoma is very rare. We studied a family bearing the constitutional chromosome translocation t(14;20)(q24;p12), 3 of whose members had a thymoma. In this family, among 27 patients, 11 had the translocation: 3 had thy- moma and 4 others had 5 different autoimmune diseases: type 1 diabetes mellitus, Graves' disease, pernicious anemia, primitive Sjogren disease, and autoimmune pancytopenia. FISH studies allowed us to be more specific about the translocation break- points. The 14q24 breakpoint was in intron 5 of RAD51L1, and the 20p12 breakpoint was 100 kb telomeric to BMP2. RAD51L1 is a tumor-suppressor gene belonging to the RAD51 family, already implicated in many tumors (uterine leiomyomas, pseudo- Meigs syndromes, pulmonary chondroid hamartomas) and involved in recombinational repair of DNA double-strand breaks. BMP2 belongs to the TGFb superfamily, and the BMP2-BMP4 genes are involved in thymocyte differentiation by blocking pro- gression from CD4� CD8� to CD4þCD8þ while maintaining a sufficient pool of immature precursors. Dysregulation of RAD51L1 and/or BMP2 may explain this familial occurrence of thymomas and autoimmune diseases. Using QRT-PCR, we studied the expression of BMP2 in 20 sporadic thymomas and found various levels of expression that may be associated with autoimmune diseases. V C 2005 Wiley-Liss, Inc.