Single-nucleotide polymorphism (SNP) describes a variation in the DNA sequence (68). Single nucleotides in the genome differ between paired chromosomes in either one individual or between two individuals. For example, the sequences TGACTA and TCACTA contain one single change in the second nucleotide from guanine (G) to cytosine (C). This results in a G and C allele for this particular gene sequence. SNPs can occur within coding or noncoding sequences of genes or in the intergenic regions. SNPs might not change the amino acid sequence of the protein that is produced (synonymous SNP) or produce a different peptide (nonsynonymous SNPs). If SNPs are located in noncoding regions, various other processes like gene splicing or transcription factor binding might be affected.
The frequency of SNPs in a given population is provided by the minor allele frequency. This frequency differs between ethnic groups and geographic locations. SNPs were associated with various human diseases including cancer disease. They also inﬂuence the effect of drug treatment and responses to pathogens and chemicals (69). SNPs are important for the comparison between genomes of different populations for examples providing information about the susceptibility of certain population to develop specific cancers (70).
The Cancer Genome Atlas Project
In 2006 the National Cancer Institute and the National Human Genome Research Institute initiated the Cancer Genome Atlas (TCGA) project. The goal of the project is to provide a comprehensive genomic characterization and sequence analysis of cancer diseases. The initial phase included glioblastoma multiforme, lung, and ovarian cancer (71,72). Many more tumor types will be added to the analysis.
The TCGA is taking advantage of high-throughput genome analysis techniques, including gene expression profiling, SNP genotyping, copy number variation profiling, genome wide methylation profiling, microRNA profiling, and exon sequencing (73). These data are accessible for researchers via the TCGA Web page (74).
The immune system plays an essential part in host defense mechanisms, in particular the response to infections and neoplastic transformation. Our increased understanding of immune system regulation provides opportunities for the development of novel immunotherapeutic and immunodiagnostic approaches.
The human immune system has the potential to respond to abnormal or tumor cells in various ways. Some of these immune responses occur in an innate or antigen-nonspecific manner, whereas others are adaptive or antigen specific. Adaptive responses are specific to a given antigen. The establishment of a memory response allows a more rapid and vigorous response to the same antigen in future encounters. Various innate and adaptive immune mechanisms are involved in responses to tumors, including cytotoxicity directed to tumor cells mediated by cytotoxic T cells, natural killer (NK) cells, macrophages, and antibody-dependent cytotoxicity mediated by complementation activation (75).
Adaptive or specific immune responses include humoral and cellular responses. Humoral immune responses refer to the production of antibodies. Antibodies are bifunctional molecules composed of a variable region with specific antigen-binding sites, combined with a constant region that directs the biologic activities of the antibody, such as binding to phagocytic cells or activation of complement. Cellular immune responses are antigen-specific immune responses mediated directly by activated immune cells rather than by the production of antibodies.
The distinction between humoral and cellular responses is historical and originates from the experimental observation that humoral immune function can be transferred by serum, whereas cellular immune function requires the transfer of cells. Most immune responses include both humoral and cellular components. Several types of cells, including cells from both the myeloid and lymphoid lineages, make up the immune system. Specific humoral and cellular immune responses to foreign antigens involve the coordinated action of populations of lymphocytes