Loss and gain of chromosomes 1, 18, and Y in prostate cancer

Nuclear suspensions of 42 prostate carcinoma specimens obtained at surgery were used to investigate loss and gain of chromosomes 1, 18, and Y by fluorescence in situ hybridization (FISH) with centromere-specific probes. The outcome of FISH analysis was correlated with clinical parameters and the relationship between DNA-FCM (ploidy at cellular level) and FISH (ploidy of individual chromosomes) was assessed. Significant loss of chromosomes 1 and 18 was infrequent (respectively, three and five cases), but 53% of the tested specimens showed loss of Y. Loss was not correlated with DNA ploidy. Significant gain occurred in 36% (chromosome 1), 63% (chromosome 18), and 28% (Y) of the specimens. Gain of chromosome 18 was shown in DNA diploid (7/14) and aneuploid tumors (18/26), while gain of chromosomes 1 and Y was nearly restricted to DNA aneuploid specimens. Significant unbalance between these chromosomes occurred in 11 cases. Most cases which had significant gain of chromosome 1 or 18 showed trisomic as well as tetrasomic cells. Simultaneous loss of some and gain of other investigated chromosomes is suggestive of clonal heterogeneity and/or multiclonality. This was observed in eight tumors. Correlation between DNA-FCM and FISH was best for the Y chromosome. DNA-FCM showed more aberrant histograms with increasing stage and grade of tumors. The presence of numerical aberrations of the investigated chromosomes however, seemed independent of clinical grade or stage

Mutations in TITF-1 are associated with benign hereditary chorea

Benign hereditary chorea (BHC) (MIM 118700) is an autosomal dominant movement disorder. The early onset of symptoms (usually before the age of 5 years) and the observation that in some BHC families the symptoms tend to decrease in adulthood suggests that the disorder results from a developmental disturbance of the brain. In contrast to Huntington disease (MIM 143100), BHC is non-progressive and patients have normal or slightly below normal intelligence. There is considerable inter- and intrafamilial variability, including dysarthria, axial dystonia and gait disturbances. Previously, we identified a locus for BHC on chromosome 14 and subsequently identified additional independent families linked to the same locus. Recombination analysis of all chromosome 14-linked families resulted initially in a reduction of the critical interval for the BHC gene to 8.4 cM between markers D14S49 and D14S278. More detailed analysis of the critical region in a small BHC family revealed a de novo deletion of 1.2 Mb harboring the TITF-1 gene, a homeodomain-containing transcription factor essential for the organogenesis of the lung, thyroid and the basal ganglia. Here we report evidence that mutations in TITF-1 are associated with BHC