%0 Journal Article
%T Evolutionary karyotypic theory of cancer versus conventional cancer gene mutation theory
%A Stepanenko A. A.
%A Kavsan V. M.
%J Biopolymers and Cell
%D 2012
%I Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine
%X For decades the conventional gene mutation cancer theory has been postulating that cancer is a genetic disease considered as a result of deterministic sequential accumulation of mutations in the handful of  driver  cancer genes occurring in a continuous linear pattern of cancer progression. However, in contrast to this postulate, recent whole genome and exome sequencing studies of primary tumor bulk and metastases or separate regions withing the same sample have revealed a large number of stochastic gene mutations for each individual with the same cancer type and significant intratumoral genetic heterogeneity with  branched evolutionary tumor growth  or  punctuated clonal evolution without observable intermediate branching  or  no dominant clones in the cancer tissue . Meanwhile, the stochastic karyotypic variation and intratumor heterogeneity are recognized to be the driving force of tumor evolution and major factors in determining relapse with acquired drug resistance. The karyotype evolution/chromosome instability and the resulting magnitude of intratumor heterogeneity significantly correlate with tumorigenic potential of cells, tumor disease progression from precancerous lesions to malignant tumors and metastases, correlate with patient survival, treatment sensitivity, and the risk of acquired resistance. Here, we discuss importance of the evolutionary karyotypic theory in understanding the cancer biology and mechanisms of tumor drug resistance.
%K tumor evolution
%K karyotype
%K chromosome instability
%K intratumor heterogeneity
%K cancer gene
%K drug resistance
%U http://www.biopolymers.org.ua/pdf/en/28/4/267/