Cancer Genomics and Proteomics

Cancer genomics and proteomics studies are dependent on different source materials for RNA and protein which can limit the studies. Source material includes the following:

• immortalized tumor cell lines: Cancer cell lines are a widely used experimental tool, and their use in cancer research has several advantages: (1) a wide spectrum of tumor types is commercially available, (2) they are easy to culture in vitro, yielding significant amounts of high-quality RNA and DNA, (3) although primary tumors are heterogeneous and invariably contaminated with normal cells, tumor cell lines are usually free of normal contamination. However, there are some drawbacks: (1) One question is how closely related they are to the primary tumors from which they originated and, even more importantly, how accurately a particular cell type represents the general population of primary tumors. In other words, they may not faithfully represent patient cancers.

• patient tumor explants:

Some possible disadvantages are (1) they are obtained as tissue masses with many different normal cell types. However, there are techniques like fluorescence activated cell-sorting (FACS) and laser capture microscopy (LCM) that can be used for obtaining patient samples. (2) patient samples represent a small and finite source of protein. However, with respect to mRNA, single patient cells can be isolated and RT-PCR can be used to amplify cDNA sequences as needed, for gene chip or cDNA microarray hybridizations.

Several goals for cancer genomics and proteomics are (1) a better understanding of cancer development, (2) providing a molecular basis for histological diagnoses, and (3) subdividing tumor types according to prognosis and response to therapy (i.e., certain proteomes may be associated with greater success with certain therapies or may represent long-term survivors)

Profiling T-cell reactive tumor antigens

Human tumor antigens recognized by CD4+ or CD8+ T cells are being classified into groups on the basis of their expression pattern. The expression pattern of the antigens is the critical factor determining their potential usefulness for cancer immunotherapy.

Cancer Immunity - Peptide Database

MHC peptides can be recovered by detergent or acid treatments of cells. They can also be obtained by transfecting tumor cells with soluble versions of MHC molecules, isolating the secreted MHC molecule and recovering the peptide.  Recovered MHC peptides can then be identified by mass spec approaches. These peptides can then be used to see whether T cells can be stimulated.

Profiling T-cell reactive tumor antigens

Aberrations in DNA methylation patters are now recognized as a hallmark of the cancer cell. In fact, methylation profiling, based on gene silencing of tumor suprressor genes, can distinguish different cancers.