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Fractional allelic imbalance in human breast cancer increases with tetraploidization and chromosome loss

โœ Scribed by Cees J. Cornelisse; Nel Kuipers-Dijkshoorn; Margreethe van Vliet; Jo Hermans; Peter Devilee


Publisher
John Wiley and Sons
Year
1992
Tongue
French
Weight
606 KB
Volume
50
Category
Article
ISSN
0020-7136

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โœฆ Synopsis


We have previously reported a complete allelotype study of 86 primary breast carcinomas, in which each non-acrocentric chromosome arm was studied with at least one polymorphic DNA-marker for the presence of allelic imbalance (Al, allelic loss or allelic gain) in the tumor. Here we report the statistical analysis of this data set, investigating the relationships between Al, DNA aneuploidy and several clinico-pathological parameters of tumor progression. Al on I 3 different chromosome arms, including 3p, I I p, and I7p, correlated significantly with the total number of Al events at other sites, suggesting that they are progression-related events. Al at I q and 16q did not show such a correlation and may thus represent earlier events. Mean fractional allelic imbalance (FAI) was significantly higher in flow cytometrically aneuploid tumors than in diploid tumors (0.27 vs. 0.17, p = 0.007), and was highest in hypotetraploid tumors (0.37). This suggests that tetraploidization followed by chromosome segregation may underlie the development of Al at multiple sites. No correlation was found between mean FA1 and clinico-pathological variables such as lymph-node involvement, stage, age, estrogen-receptor content and development of distant metastases, although there was a noticeable trend towards impaired survival for those patients with a higher-thanmedian FA1 value.


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