Aneuploidy, stem cells and cancer.

Abstract

Telomeres which protect the individual chromosomes from disintegration, end-to-end fusion and maintain the genomic integrity during the somatic cell divisions play an important role in cellular aging. Aging and cancer development are linked with each other because cancer is considered a group of complex genetic diseases that develop in old cells and, in both, telomere attrition is involved. Numeric chromosome imbalance also known as aneuploidy is the hallmark of most solid tumors, whether spontaneous or induced by carcinogens. We provide evidence in support of the hypothesis that telomere attrition is the earliest genetic alteration responsible for the induction of aneuploidy. Dysfunctional telomeres are highly recombinogenic leading to the formation of dicentric chromosomes. During cell divisions, such complex chromosome alterations undergo breakage fusion bridge cycles and may lead to loss of heterozygosity (LOH) and gene amplification. Furthermore, we have provided evidence in support of the hypothesis that all types of cancer originate in the organ- or tissue-specific stem cells present in a particular organ. Cancer cells and stem cells share many characteristics, such as, self-renewal, migration, and differentiation. Metaphases with abnormal genetic constitution present in the lymphocytes of cancer patients and in some of their asymptomatic family members may have been derived from the organ-specific stem cells. In addition, evidence and discussion has been presented for the existence of cancer-specific stem cells. Successful treatment of cancer, therefore, should be directed towards these cancer stem cells.