Ongoing phenotypic and genotypic variation in cancer cell lines under varied culture conditions

Abstract

During cancer cell development large numbers of interstitial loss-of-heterozygosities (LOHs) along with gain-of-heterozygosities (GOHs) occurs during different stages of cancer development, but how often these changes occur and vary in response to varied culture condition causing a functional impact on the cancer cell phenotypes still need investigation. Using the next-generation sequencing (NGS)-based AluScan platform, forward and reverse mutation characterized by GOH followed by LOH type of single-nucleotide-variations (SNVs) were found in cancer cell lines under normal culture conditions microenvironment. However, the presence of varied culture condition, for example, different range of pH and anti-cancer drugs shows an Increase in diversity among cancer cells at the cellular, genetic and phenotypic levels. All cancer cell lines under varied culture condition show an increase in the production of daughter number variation increasing cellular diversity, and more frequent forward and reverse mutation cycles among different cell lines. These genotypic variations caused functional changes in cancer cell phenotype as fluctuation in population doubling time and occurrence of different cell type were observed. Certain cell type increment in population also increases cellular adhesion. Interestingly, chemical induction brought about different extents of phenotypic and genotypic variation in all four cell lines suggesting the factors determining the extent variations varied between cell lines. Moreover, these phenotypic and genotypic variations occur simultaneously aiding cancer cell survival and development explaining the adaptive mechanism in cancer cells during developmental stages.

Date of Award	2019
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology