New Bioinformatics Method Leads to More Precise Way to Target Tumor Growth

Highlights

• Acquired mutations are the most common cause of cancer.
• Identifying genes that cause cancer when altered is often challenging.
• New bioinformatics software to identify cancer-causing genes developed.

There are numerous methods to spotlight the so-called cancer driver genes - but a question remains -- which of the techniques produce the most accurate results? A team of Johns Hopkins computational scientists and cancer experts have devised a bioinformatics software to evaluate how well the current strategies identify cancer-promoting mutations and distinguish them from benign mutations in cancer cells.

"Identifying cancer-causing genes is often challenging, but is critical for directing research along the most fruitful course," said Bert Vogelstein, a member of the Ludwig Center at the Johns Hopkins Kimmel Cancer Center and one of the journal article's co-authors. "This paper establishes novel ways to judge the techniques used to identify true cancer-causing genes and should considerably facilitate advances in this field in the future."

Bioinformatics software for driver gene prediction and a framework for evaluating and comparing other cancer mutation prediction methods were developed. The tool was applied to 8 existing cancer driver gene prediction methods.

The results were not entirely reassuring. "Our conclusion," Tokheim said, "is that these methods still need to get better. We're sharing our methodology publicly, and it should help others to improve their systems for identifying cancer driver genes."

The lead author of the article was Collin J. Tokheim, a doctoral student in the Institute of Computational Medicine and the Department of Biomedical Engineering, which are both shared by the university's Whiting School of Engineering and its School of Medicine. He was supervised by his doctoral adviser, Rachel Karchin, an associate professor of biomedical engineering and oncology, the William R. Brody Faculty Scholar and a core faculty member of the university's Institute for Computational Medicine. Karchin, who also is a member of the Kimmel Cancer Center, was the senior author of the journal article.

Genetics of Cancer

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Genes are present in the DNA in each cell that makes up your body. Genes control the cells’ working by making proteins with specific function and act as messengers for the cell.

Cancers begin when 1 or more genes in a cell are mutated or changed. This results in an abnormal protein or no protein production at all. The abnormal protein causes the cells to multiply uncontrollably and become cancerous. One mutation is unlikely to lead to cancer; multiple mutations over a lifetime cause cancer.

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The two types of genetic mutations are

1. Acquired mutations occur due to damage to genes during a person’s life. It is one of the common cause of cancer.

2. Germline mutations are passed from a parent to a child and are less common

Gene Mutations Linked to Cancer

Genes that contribute to cancer development fall into 3 broad categories

I. Tumor suppressor genes are known as protective genes. They limit cell growth by looking how the cells divide into new cells, repairing mismatched DNA and controlling when a cell dies. When there is a mutation in the tumor suppressor gene there is uncontrollable cell growth and leads to tumor. Examples of tumor suppressor gene include BRCA1, BRCA2, and p53.

Mutations in BRCA1, BRCA2 increase a woman’s risk of developing breast or ovarian cancers. p53 is the most commonly mutated gene in people who have cancer. 50% of cancer cases involve a missing or damaged p53 gene.

II. Oncogenes turn a healthy cell into cancerous cell. Oncogene mutations are not inherited. Common oncogenes include

HER2 protein controls cancer growth and spread such as ovarian and breast cancers

Ras family of genes which make proteins involved in cell communication pathways, cell growth, and cell death.

III. DNA repair genes fix mistakes when DNA is copied. If there is an error in the DNA repair gene the errors are not corrected thereby they become mutations which lead to cancer. DNA repair gene mutations are inherited such as Lynch syndrome (inherited disorder that increases the risk of many types of cancer).

References

1. Collin J. Tokheim et al. Evaluating the Evaluation of Cancer Driver Genes; PNAS; (2016) DOI: 10.1073/pnas.1616440113
2. Cancer Genetics - (http://www.cancer.net/navigating-cancer-care/cancer-basics/genetics/genetics-cancer)

Source-Medindia