The Heterogeneity And Genomic Variation In Different Tumor Cell Populations Of Lung Cancer Tissue

Tumorigenesis is often thought as a biology evolution process of tumor cell populations. As a collection of rogue cells with multiple distinct phenotypes, tumor often origins from the colonial expansion of deregulated cells originated from normal tissues. During such a process, the tumor accumulates more and more genetic mutations. With the accumulation of genetic variation and the heterogeneity of microenvironments, tumor cell population will often display substantial amount of heterogeneity, which causes the fitness and reproduction rate of tumor cell population to change.In order to test the genetic diversity between different tumor cell populations and between tumor and normal cell populations, we choose a non-small cell lung cancer case from Beijing tumor hospital. We hope to find the key genes which change the fitness of the tumor cell population and identify the biological function of the key genes. We constructed three exon-capture DNA sequencing libraries. With the help of the next generation sequencing technology (Solexa platform) we got three exome dataset from C31-2, C72-2and blood sample. Using bioinformatic tools, we analysised the raw data of exome sequencing, and screened the SNP site information across the three samples. Finally, we selected40reliable SNP sites to check point mutation rates among all the17samples. According to the results, we found35SNP point mutation sites which had significant difference in mutation rates among all the normal and tumor samles. Overall, the mutation rate is more high in tumor cells than in normal cells. We found there were15SNP sites which existed almost among all the tumor cell populations. And there were12and6specific SNP sites in sample C31-2, C72-2respectively. We conclude that the tumor population may origin from one common ancestral cell line. In the evolution process, the subsequent population gets more new mutations, and becoming more and more heterogeneous.Using the bioinformatic software gene anno, we found there were34SNP sites existing in the CDS region and another one existing in the splicing site. In order to shed more light on the function of the muted gene function (SNP region), we upload the34genes set to the KEGG database. Luckily, we found there were two genes which involved in the process of non-small lung cancer pathway. They are PI3KCA and TP53gene which played an important role in the development of lung cancer. At the same time, we upload the34genes set to the PANTHER online database; we found many genes involved in the process of response to stimulus, cellular process, regulation of biological process and cell communication. We guess the two key gene may changed the fitness of the tumor population and accelerated the cloned expansion of tumor cell population.