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Familial occurrence of thymoma and autoimmune diseases with the constitutional translocation t(14;20)(q24.1;p12.3)
Author(s) -
Nicodème Frédéric,
Geffroy Sandrine,
Conti Massimo,
Delobel Bruno,
Soenen Valérie,
Grardel Nathalie,
Porte Henri,
Copin MarieChristine,
Laï JeanLuc,
Andrieux Joris
Publication year - 2005
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20225
Subject(s) - thymoma , chromosomal translocation , biology , immunology , cancer research , medicine , gene , genetics
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 thymoma and 4 others had 5 different autoimmune diseases: type 1 diabetes mellitus, Graves' disease, pernicious anemia, primitive Sjögren disease, and autoimmune pancytopenia. FISH studies allowed us to be more specific about the translocation breakpoints. 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 TGF β superfamily, and the BMP2 – BMP4 genes are involved in thymocyte differentiation by blocking progression from CD4−CD8− to CD4+CD8+ 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. © 2005 Wiley‐Liss, Inc.