Breast cancer is the most common cancer among women worldwide, and with 521,900 deaths in 2012, also has the highest mortality (Torre, et al. 2015). In the United States, the overall five-year-survival rate for breast cancer patients is about 89%, but ranges from almost 100% when diagnosed with stage I to as low as 25% for stage IV (Howlader, et al. 1975-2014). Clinical and histological parameters, the aggressiveness of individual tumors, and the response of patients to systemic therapy are more variable in breast cancer than in many other types of cancer (Bettaieb, et al. 2017). Non Inherited (somatic) mutations in the TP53 gene are much more common than inherited mutations, occurring in 20 to 40 percent of all breast cancers. These somatic mutations are acquired during a person's lifetime and are present only in cells that become cancerous. The cancers associated with somatic mutations do not occur as part of a cancer syndrome. Most of these mutations change single protein building blocks (amino acids) in the p53 protein, which reduces or eliminates the protein's tumor suppressor function. This altered p53 protein cannot regulate cell proliferation effectively. Specifically, it is unable to trigger apoptosis in cells with mutated or damaged DNA. As a result, DNA damage can accumulate in cells. Such cells may continue to divide in an uncontrolled way, leading to tumor growth.

Compared with breast cancers without TP53 gene mutations, tumors with these genetic changes tend to have a poorer prognosis: They are more likely to be aggressive, to be resistant to treatment with certain anticancer drugs and radiation, and to come back (recur) after treatment. About 5% to 10% of breast and 10% to 15% of ovarian cancers are hereditary. Hereditary cancer means cancer runs in your family, and could be caused by a change in certain genes that you inherited from your mother or father. Out of the 563 associated genes, we will focus on 2 major genes responsible for Breast Cancer, which are TP53 and BRCA 1 / 2.

Inherited changes in the TP53 gene greatly increase the risk of developing breast cancer, as well as several other forms of cancer, as part of a rare cancer syndrome called Li-Fraumeni syndrome (described below). These mutations are thought to account for only a small fraction of all breast cancer cases. Non Inherited (somatic) mutations in the TP53 gene are much more common than inherited mutations, occurring in 20 to 40 percent of all breast cancers. These somatic mutations are acquired during a person's lifetime and are present only in cells that become cancerous. In this tutorial, we will carry out hands-on analysis on the dataset provided in the research article we recently discussed, i.e.,  (Refer to the research article here: https://pubmed.ncbi.nlm.nih.gov/29181861/). We will understand how the input file should look like, run the educational pipeline with steps mentioned, visualize the results and interpret biological insights.

Click on the link to the Bioproject here: https://www.ncbi.nlm.nih.gov/bioproject/PRJNA399503

You can run the demo pipeline on the T-Bioinfo Server to learn the flow of steps in the pipeline and visualize the results obtained: https://server.t-bio.info/pipelinesmutationvariant/new?tags=MutationVariant-RmodelGenomeGTF-fastA-SE

To get more insights about the project, run the pipelines and learn to interpret results, you can visit the example project on the OmicsLogic Learn Portal: https://learn.omicslogic.com/courses/course/project-14-breast-cancer-oncogene-variant-calling