RESUMO
The mouse strain CBA/CaH-T(14;15)6Ca/J carries a homozygous balanced reciprocal translocation between mouse chromosomes 14 and 15, but the break points of this translocation have not previously been examined in detail. Using fluorescent in situ hybridization, we assigned the break point in 14qE3 to a 200-kb region devoid of any known gene. We similarly defined the break point in 15qA1 to a 27-kb region containing involving ADAMTS12. The chromosomal break likely is between exons 2 and 3 of ADAMTS12. This gene encodes a disintegrin and metalloproteinase with thrombospondin motifs, and this product plays crucial roles in both vascularization and cancer progression and has been implicated in the development of arthritis. The CBA/CaH-T(14;15)6Ca/J mouse strain likely is a suitable model for further examination of the influences of defective ADAMTS12 in various pathologic processes.
Assuntos
Proteínas ADAM/genética , Quebra Cromossômica , Cromossomos de Mamíferos , Camundongos Endogâmicos , Proteínas ADAM/metabolismo , Proteínas ADAMTS , Animais , Células Cultivadas , Modelos Animais de Doenças , Éxons , Feminino , Fibroblastos/citologia , Fibroblastos/metabolismo , Expressão Gênica , Humanos , Hibridização in Situ Fluorescente , Masculino , Camundongos , Camundongos Endogâmicos CBARESUMO
Alterations of chromosome bands 19p13 and 19q13 in the form of added extra material of unknown origin are among the most frequent cytogenetic changes in ovarian carcinomas. To investigate the chromosomal composition of the 19p+ and/or 19q+ markers, we selected for examination 26 ovarian carcinomas which by G-banding had one to four 19p+ and/or 19q+, in total 37 markers. These cases were then subjected to chromosomal microdissection with subsequent reverse painting, which gave informative results on 29 markers. The breakpoints on chromosome 19 were located in both the short (p; n = 15) and the long (q; n = 10) arms, as well as in the centromeric (n = 2) and pericentromeric (n = 6) region. The analysis showed that many chromosomes added material to chromosome 19, but the chromosome arms 11q, 21q, and 22q were particularly common donors. Homogeneously staining regions (hsr) were seen in only three markers, in all of them consisting of 19p material. Eighteen markers were derived from an unbalanced translocation involving chromosome 19. In five markers, chromosome 19 was rearranged with two chromosomes. The most complex marker showed chromosome 19 rearranged with three other chromosomes, i.e., X, 13, and 16. In five markers, all of the additional material stemmed from chromosome 19 itself. This is the first large chromosome microdissection/FISH study of chromosome 19 markers in ovarian carcinomas. A detailed map of the rearrangements should provide clues to the positions of oncogenes and potential fusion genes important in ovarian carcinogenesis.
Assuntos
Coloração Cromossômica/métodos , Cromossomos Humanos Par 19/genética , Rearranjo Gênico , Neoplasias Ovarianas/genética , Adenocarcinoma de Células Claras/genética , Bandeamento Cromossômico , Quebra Cromossômica , Mapeamento Cromossômico , Cistadenocarcinoma/genética , Feminino , Humanos , Cariotipagem , Microdissecção , Ovário/metabolismo , Translocação Genética/genéticaRESUMO
A boy with signs of Klinefelter syndrome, mild facial dysmorphic features, and severely retarded speech development displayed a female karyotype with mosaicism for two marker chromosomes 48,XX,+mar1,+mar2[68]/47,XX,+mar1[19]/47,XX,+mar2[6]/46,XX[8]. Using chromosomal microdissection, locus-specific fluorescence in situ hybridization (FISH), and PCR with several Y-chromosome markers, the larger supernumerary marker chromosome (SMC) was characterized as a ring Y-chromosome. Detection of the SRY-region explained the male phenotype. The smaller second marker chromosome contained the pericentromeric region of chromosome 8. We suggest that the co-occurrence of a partial Y-chromosome and partial trisomy 8 explain the severe speech delay and the facial dysmorphic features.