Cancer Transcriptome Diagnostics

Cancer is constantly changing and methods to detect those changes can be very important. By looking at the entire cancer transcriptome it can quickly tell what expression changes have happened in the cancer.

Kathy Liszewski wrote an interesting article on this in Genetic Engineering News which will be briefly summarized here.

RNA and Cancer

Also, by looking at how RNA expression is changing, it can give information on how the cancer will respond to different therapies in addition to giving information on their oncogenic properties.

Disruption of RNA at different points in its life or in different ways can lead to or make a difference in cancers.

Radiation exposure can lead to  fusion oncogenes, some affecting the MAPK pathways and others caused overexpression of a nuclear receptor that is connected with malignancy.

RNA Variety

One new area of research is looking at the many modifications of RNA of which 110 are known so far. Something as simple as a change in methylation can change everything. It can affect where it goes, its interpretation, and affect stability. All can help lead to cancer.

This has allowed new diagnostic indicators to be found that can give an indication of time until relapse.

RNA Editing

The amount of RNA editing that goes on in the body is just beginning to be appreciated. It allows changes in proteins  that will change the function. Interestingly, different tissues in the body can have different RNA editing profiles. Dr. Li of Stanford thinks that there may be more editing enzymes in cancer tissue.

He found an example of this in human heptocellular carcinoma increased the tumor initiating potential of a protein.

The Cancer Genome Atlas should help researchers. It does large scale sequencing of cancers and then distributes the data to researchers.

APOBEC

There is a family of 9 DNA editing enzymes (APOBEC) that aid in viral immunity. Some of the 9 also help diversify antibody gene DNA and also edit mRNA. Although 4 of the family can target retroviruses like HIV-1, one of them, APOBEC3B can interfere. Dr. Reuben Harris of the Masonic Cancer Center hypothesized that APOBEC3B would be an important cause or factor in a wide range of cancers.

His research showed its involvement in mutagenesis in many cancers and was corroborated by separate research done by Drs. Gordenin and Stratton. So this may lead to useful diagnostic tests and identify cancers that are more difficult to treat and help suggest targeted treatments.

MicroRNAs

MicroRNAs are critical for normal tissue functioning. Many of them though are found in regions of the genome that are fragile. As cancer progresses the functioning of the microRNAs is changed.

Two microRNAs, miR-143 and miR-145 have been found to be  greatly reduced in colon cancer and both are in the 5q32 chromosome.

SKIP and Apoptosis

The enzyme complex, RNA polymerase II catalyzes DNA transcription. It sometimes stops and needs SKIP to get restarted. SKIP is Ski-interacting protein.  That part is good, but SKIP can also help cancer cells survive. Dr. Katherine Jones found that by reducing SKIP, it increased the likelihood of p53-mediated apoptosis. So if small molecule SKIP inhibitors can be found, chemotherapy agents can become more effective.