title: Familial occurrence of thymoma and autoimmune diseases with the constitutional translocation t(14;20)(q24.1;p12.3).
abstract: 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 TGFbeta 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.
authors.affiliation: Laboratoire de Génétique Médicale, Hôpital Jeanne de Flandre, CHRU, Lille, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Nicodème
authors.forename: Sandrine
authors.initials: S
authors.lastname: Geffroy
authors.forename: Massimo
authors.initials: M
authors.lastname: Conti
authors.forename: Bruno
authors.initials: B
authors.lastname: Delobel
authors.forename: Valérie
authors.initials: V
authors.lastname: Soenen
authors.forename: Nathalie
authors.initials: N
authors.lastname: Grardel
authors.forename: Henri
authors.initials: H
authors.lastname: Porte
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Copin
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Laï
authors.forename: Joris
authors.initials: J
authors.lastname: Andrieux
mesh_terms: D001327:Autoimmune Diseases / Q000235:genetics*; D001483:Base Sequence; D002883:Chromosomes, Human, Pair 14; D002890:Chromosomes, Human, Pair 20; D017931:DNA Primers; D005260:Female; D006801:Humans; D008297:Male; D010375:Pedigree; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013945:Thymoma / Q000235:genetics*; D013953:Thymus Neoplasms / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: D017931:DNA Primers