Aneuploidy In Cancer Cells Research Articles

Mitoses and cancer

Mitoses are coupled to cell proliferation. In non-neoplastic cells they are usually symmetric and typical and lead to increase in cell number. Cancer cells are notorious for their asymmetric divisions, which are considered to reflect abnormalities due to disordered growth. The centrosome controls the mitotic activity and it has been proposed that centrosomal defects possibly contribute to carcinogenesis and aneuploidy of cancer cells. So far the atypical mitoses often seen in neoplastic cells are not considered unique. However careful observation of atypical mitoses in various neoplasms revealed that although they were indeed “atypical” they resembled each other within the same tumor and were different from those of other tumors. It is proposed that specific centrosomal alterations, which lead to a limited variety of atypical mitotic figures in each neoplasm, are not a random result but a distinct event that is possibly involved in carcinogenesis.

P53 mutations and DNA ploidy in colorectal adenocarcinomas.

The p53 tumour suppressor gene has an important role in the the maintenance of genome stability and its mutational inactivation may be at the origin of aneuploidy in cancer cells. The aim of this study was to determine whether p53 mutations were associated to DNA aneuploidy, as assessed by flow cytometry, in colorectal adenocarcinomas. Analysis of p53 mutations spectrum of the sorted nuclei was done by Denaturing Gradient Gel Electrophoresis (DGGE) and DNA sequencing. Overall, we studied 20 adenocarcinomas, the corresponding control mucosa, and 7 lymph node metastases. Five tumours (25%) were DNA diploid, while 15 tumours (75%) were composed of DNA aneuploid and diploid subpopulations. DNA diploid control mucosa and adenocarcinomas showed no p53 mutations, while 60% of the tumours with DNA aneuploidy had p53 mutations. Therefore, p53 mutations occurred significantly more often in DNA aneuploid than in DNA diploid tumours (p < 0.04, Fisher’s exact test). Incidences of DNA aneuploidy and p53 mutations in lymph node metastases were 60 and 86%, respectively. In all tumours showing a p53 mutation, the wild-type allele was not or only bearly visible in DNA aneuploid cells suggesting that, in such cells, aneuploidy is accompanied by complete p53 functional inactivation. The present observations suggest that p53 mutations may have a role in the origin of aneuploidy at late stages of colorectal carcinogenesis.