Karyotypic abnormalities

Cheng Q, Yang W, Raimondi SC et al. Karyotypic abnormalities create discordance of germline genotype and eancer cell phenotypes. Nat Genet 2005 37 878-882. 

Transformation Cell changes manifested by escape from control mechanisms, generally resulting in increased growth potential, alterations in the cell surface, and karyotypic abnormalities. Cell transformation generally occurs as a result of the acquisition of genetic information as by a virus entering the cell. 

Ph was the first karyotypic abnormality specifically implicated in the pathogenesis of cancer its discovery has resulted in extensive research into the molecular biology of CML. This chromosomal abnormality is characteristic of CML and is present in 90% to 95% of patients with a presumptive diagnosis of the disease. It can also occur in as many as 20% of adults and 5% of children with acute lymphoblastic leukemia, and in as many as 5% of adults and children with acute myelogenous leukemia. ... 

As mentioned earlier in this discussion, CDK4 and MDM2 immunostains can be utilized to help confirm the adipocytic nature of some problematic soft tissue tumors (namely, dedifferentiated liposarcoma). However, de Vreeze and colleagues have shown that MLPS and round-cell liposarcoma of the extremities typically lack these determinants immunohistochemically. This reflects the fact that such lesions manifest karyotypic abnormalities that are different from well-differentiated and dedifferentiated liposarcomas. ... 

Wilms tumor Triphasic blastemal, epithelial, and stromal components. Blastemal cells small, round or oval, in nodules or serpentine patterns. Epithelial component primitive rosette-like to tubular or papillary. Mesenchymal component fibrous, myoid, adipose, chondroid, osseous, neural. Blastemal vimentin, desmin. Epithelial cytokeratin. Mesenchymal variable according to differentiation pattern. Various abnormalities including mutations of WT1 at 11 pi 3 and WT2 at 11 pi 5 numeric and structural karyotypic abnormalities of chromosomes 1, 11, 13, 14, 16, 1 7, 19, and 22. 

Mechanical, enzymatic, and chemical cell dissociation methods are currently used as passaging techniques for hPSCs. However, these methods are not well defined, which introduces variability into the system and may lead to cell damage. The enzymatic detachment of cells from dishes sometimes generates karyotype abnormalities. 

While all chromosomal abnormalities can In principle be detected by prenatal diagnosis, fetal karyotyping Is not at present being done as a general screening procedure Rather,... 

During mitosis, aU the DNA is highly condensed to allow separation of the sister chromatids. This is the only time in the ceE cycle when the chromosome structure is visible. Chromosome abnormalities may be assessed on mitotic chromosomes by karyotype analysis (metaphase chromosomes) and by banding techniques (prophase or prometaphase), which identify aneu-ploidy, translocations, deletions, inversions, and duplications. 

Klinefelter syndrome (47,XXY) is seen in approximately 1 in 1,000 males (all individuals with this condition have a male phenotype because they have a Y chromosome). Klinefelter males are nearly always sterile because of atrophy of the seminiferous tubules. They tend to be taller than average, with abnormally long arms and legs. Breast development (gynecomastia) is seen in about one third of cases, and the IQ is on average 10-15 points below that of unaffected siblings. Individuals have also been seen with 48.XXXY and 49,XXXXY karyotypes the additional X chromosomes produce a more severely affected phenotype. 

Several other types of structural abnormalities are seen in human karyotypes. In general, their frequency and clinical consequences tend to be less than those of translocations and deletions. 

Veldman, T., Vignon, C., Schrock, E., Rowley, J. D., and Reid, T. (1997) Hidden chromosome abnormalities in hematological malignancies detected by multi-colonr spectral karyotyping. Nat. Genet. 15, 406 10. 

There has been much discussion about the potential utility of flow cytometry of chromosomes for clinical diagnosis. As regards its sensitivity, this technique appears to stand somewhere between the technique of flow analysis of whole cells for DNA content and that of microscope analysis of banded chromosomes. It may be a useful intellectual exercise for readers to ask themselves which technique or techniques would be most appropriate for detecting the following types of chromosome abnormalities (1) tetraploidy, where the normal chromosome content of cells is exactly doubled because of failure of cytokinesis after mitosis (2) an inversion in an arm of one particular chromosome and (3) trisomy (the existence of cells with three instead of two) of one of the small chromosomes. In addition to these limitations, the use of flow cytometry to look for abnormal chromosomes has been confounded by the fact that several human chromosomes are highly polymorphic, and flow karyotypes, therefore, vary considerably among normal individuals. 

Pseudodiploid This describes the condition where the number of chromosomes in a cell is diploid but, as a result of chromosomal rearrangements, the karyotype is abnormal and linkage relationships may be disrupted. 

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