CGH

Micropapillary carcinoma of the breast is associated with increased rates of lymph node metastasis and lymphovascular invasion. While activating point mutations in PIK3CA (encoding phosphatidylinositol-3-kinase catalytic subunit) or AKT1 are found in 25% to 30% of invasive ductal carcinomas, the mutational profile of invasive micropapillary carcinomas has not been characterized in detail. Micropapillary carcinomas, concurrent metastatic and precursor breast lesions from 19 patients were identified. Lesional tissue was punched from paraffin-tissue blocks, and genomic DNA was extracted and screened for a large panel of known hotspot mutations using multiplex polymerase chain reaction and mass-spectroscopy analysis (643 mutations in 53 genes). Hotspot point mutations were identified in 35% (7/20) of micropapillary breast carcinomas, including PIK3CA exons 7, 9 and 20 hotspots, as well as the AKT1 plekstrin homology domain mutation (E17K); mutations in TP53 and KRAS were each found in a...

The cane toad (Bufo marinus) is one of the most notorious animal pests encountered in Australia. Members of the genus Bufo historically have been regarded as having genotypic sex determination with male homogamety/female heterogamety. Nevertheless, as with many toads, karyotypic analyses of the cane toad have so far failed to identify heteromorphics sex chromosomes. In this study, we used comparative genomic hybridization, reverse fluorescence staining, C-banding, and morphometric analyses of chromosomes to characterize sex chromosome dimorphism in B. marinus. We found that females consistently had a length dimorphism associated with a nucleolus organizer region (NOR) on one of the chromosome 7 pair. A strong signal over the longer NOR in females, and the absence of a signal in males indicated sex-specific DNA sequences. All females were heterozygous and all males homozygous, indicating a ZZ/ZW sex chromosomal system. Our study confirms the existence of sex chromosomes in this species. The ability to reliably identify genotypic sex of cane toads will be of value in monitoring and control efforts in Australia and abroad.

Purpose: 1p36 deletion syndrome is the most common terminal deletion syndrome, with an incidence of 1/5,000 newborns. But 22q13 duplications seem to be exceedingly rare. A combined 1p36 deletion and 22q13 duplication was more rarely observed and presented variability of clinical features, which increases the importance of reporting additional cases in order to better characterize genotype-phenotype correlations.

Methods: A boy and a fetus from a single family with combined 1p36 deletion and 22q13 duplication characterized by array CGH and MLPA were described here.

Results: The proband presented severe developmental delay, hypotonia, epilepsy, feeding difficulties with failure to thrive, tracheal malformation,
clinodactyly, strephexopodia, fair skin, facial dysmorphism and died at 1 year of age. Array CGH uncovered a 9.3-Mb deletion of 1p36 plus a 6.655-Mb duplication of 22q13in the proband. This rearrangement was confirmed by MLPA. When his mother was pregnant again, array CGH detected an almost identical rearrangement with that of the proband. She terminated the pregnancy at 24 weeks gestation. The fetus was female and had similar facial dysmorphism as the proband. Karyotypes of parents are all normal.

Conclusions: Most of the features in the proband were similar to those associated with both isolated 1p36 deletions and 22q13 duplications.
However, tracheal malformation, fair skin and strephexopodia were only observed in our patient. Given that 22q13 duplications are rare and not as well characterized as 1p36 deletions, we attributed these features to 22q13 duplications. Importantly, we emphasize importance of prenatal diagnosis of females who had such abnormal pregnancy.

Complex karyotypes are seen in approximately 15% of de novo MDS/AML and in up to 50% of therapy-related MDS/AML. These patients represent a therapeutic challenge for which no current treatment approach is satisfactory. Therefore, a large number of genetic studies using cytogenetic molecular techniques have been performed to better define the chromosomal abnormalities in this poor-prognosis group. On the basis of the available data from several studies of AML with complex karyotypes, similar findings on recurrent breakpoints and frequently lost and gained chromosomal regions have been observed. The most frequent rearrangements, in all the published series, were unbalanced translocations leading to loss of chromosomal material. Overall, loss of 5q and/or 7q chromosomal material seemed the more common event, and losses of 5q, 7q, and 17p in combination were observed in many cases. Overrepresented chromosomal material from 8q, 11q23, 21q and 22q was found recurrently and in several cases this was due to the amplification of the MLL (located at 11q23) and AML1/RUNX1 (located at 22q22) genes. As a result of these findings, the presence of MLL copy gain/amplifications or losses of the short arm of chromosome 17, in association with 5/5q, have been found to be indicators of an extremely poor prognosis. Interestingly, this non-random pattern of DNA gains and losses, that characterizes AML cases with complex karyotypes, affects the gene expression pattern, and a specific expression profile, characterized by the upregulation of genes involved in the DNA repair and chromosome segregation pathways, has been recently reported. Therefore, a comprehensive genome-wide analysis of patients with AML or MDS with complex karyotypes has led to a better characterization of chromosomal aberrations. These specific alterations could be used in the near future as therapeutic targets or markers for the risk stratification of patients, detection of minimal residual disease and the development of new therapeutic interventions. Copyright © 2005 John Wiley & Sons, Ltd.

In this paper a new holographic D display system based on computer-generated hologram (CGH) is developed for the reconstruction of 3D objects. A new algorithm is also developed to reduce the hologram computation time and memory usage. The dynamic 3D objects are successfully reconstructed at video rates in both real and virtual spaces.