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TRISOMY 8 MOSAICISM: CELL CYCLE KINETICS AND ...

TRISOMY 8 MOSAICISM: CELL CYCLE KINETICS AND ...

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original finding of La Marche in their patients with T8m. The growth advantage of<br />

normal cells over the trisomic cells resulted in the decrease of trisomic cells and lead to<br />

the complete disappearance of trisomic cells over time (Mark and Bier 1997).<br />

Support for selective growth advantage of normal cells is evident from the<br />

decrease of trisomy 8 cells from interphase to metaphase found in the transformed blood,<br />

peripheral blood, umbilical cord, and chorion (Table 3). The significant difference<br />

suggests there is a mechanism resulting in the decrease of trisomic cells in metaphase.<br />

Alpha-satellite probes used in the FISH interphase study are known to give a large signal<br />

and hence have a greater chance of overlap within the cell (Moore et al. 2000). The<br />

sensitivity of the DNA probes has been reported as 80-90% efficiency for detecting the<br />

specific region if present on the chromosome (Moore et al. 2000 and Ruangvutilert et al.<br />

2000). Therefore, the efficiency of FISH probes would explain a decrease in trisomic<br />

interphases compared to metaphase, but would not explain the reverse.<br />

Mechanisms<br />

Mechanisms that may be responsible for the significant decrease in trisomy 8<br />

metaphases include varying cellular growth rates, apoptosis or cell death, and entry into<br />

the GO phase. First we suggested a growth rate difference between the normal and<br />

trisomy 8 cells. Trisomy 8 cells may have a more difficult time undergoing mitosis due<br />

to the extra chromosome and therefore genetic information imbalance, while the normal<br />

cells would divide as usual. This would possibly slow down the division rate since<br />

replication, chromosomal alignment, and division times must be in synchrony for proper<br />

cellular division. Growth disadvantage has been reported in a comparison of 45,X and<br />

35

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