This web page was produced as an assignment for Genetics 564, an undergraduate capstone course at UW-Madison.
What is ovarian cancer?
Ovaries are the reproductive glands found in the female reproductive system. The ovaries produce eggs, known as ova, for reproduction. They are also the main source of the hormones estrogen and progesterone [1]. There are more than 30 types of ovarian cancer. These types are categorized based on the cells from which they originate. The three most common cell types in which cancerous tumors start are surface epithelium, germ cells, and stromal cells [2]. Epithelial ovarian tumors develop in the on the outer surface of the ovary. This type of tumor is generally benign; however, cancerous epithelial tumors, called "carcinomas" are the most common and most dangerous form of ovarian cancer, accounting for 85-90% of ovarian cancer cases [1]. Germ cell tumors develop in the cells that produce ova in the ovaries. Like epithelial tumors, ovarian germ cell tumors are often benign, but they can sometimes be cancerous and therefore life-threatening. Even so, 90% of patients with germ cell malignancies can be cured with their fertility protected. Stromal tumors develop in the connective tissue in the ovary and are rare, representing only 2% of ovarian cancer cases [2]. |
What is epithelial ovarian cancer?
Neoplasms from the surface epithelium of the ovary contain a wide variety of what is called "Müllerian-type cells', including serous, mucinous, endometrioid, and clear cell. In the western world, epithelial ovarian cancer is the most lethal gynecologic cancer, accounting for more deaths than endometrial and cervical cancer combined. One reason for the high mortality rate is that the vast majority of women are diagnosed with at state 3, where the cancer has spread to other areas of the abdomen. Also contributing to the high mortality is the advanced age at diagnosis (around 63 years of age), with an increase after menopause. While ultrasounds are useful for locating some sites of the disease, surgical evaluation is necessary for accurate staging and to remove large tumors. However, surgery is rarely able to render patients disease free, and postoperative chemotherapy is usually required [3].
Neoplasms from the surface epithelium of the ovary contain a wide variety of what is called "Müllerian-type cells', including serous, mucinous, endometrioid, and clear cell. In the western world, epithelial ovarian cancer is the most lethal gynecologic cancer, accounting for more deaths than endometrial and cervical cancer combined. One reason for the high mortality rate is that the vast majority of women are diagnosed with at state 3, where the cancer has spread to other areas of the abdomen. Also contributing to the high mortality is the advanced age at diagnosis (around 63 years of age), with an increase after menopause. While ultrasounds are useful for locating some sites of the disease, surgical evaluation is necessary for accurate staging and to remove large tumors. However, surgery is rarely able to render patients disease free, and postoperative chemotherapy is usually required [3].
Symptoms [4]
The following are symptoms that are associated with ovarian cancer:
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Treatment
Ovarian cancer is treated with combination of chemotherapy and surgery. In early stage ovarian cancer, surgery involves removing the ovary and potentially the fallopian tube, allowing the potential for future reproduction. In late stage ovarian cancer, surgeons remove both ovaries, fallopian tubes, and sometimes the uterus, as well as nearby lymph nodes where the cancer may have spread. Chemotherapy is often used in conjunction with surgery to kill any cancer cells that may be remaining after the procedure [5]. |
What role does TP53 play in ovarian cancer?
Somatic mutations in the TP53 gene occur in almost half of all ovarian cancers. TP53 encodes for the protein called p53, a tumor suppressor that helps keep cells from growing and dividing uncontrollably. Most of these mutations change single amino acids in the p53 protein, which reduces or eliminates the protein's tumor suppressor function. Because the altered protein is less able to regulate cell growth and division, a cancerous tumor can develop [6].
The p53 protein is located in the nucleus and binds directly to DNA. When the DNA in a cell becomes damaged by agents such as toxic chemicals, radiation, or ultraviolet (UV) rays from sunlight, p53 plays a critical role in determining whether the DNA will be repaired or whether the damaged cell will undergo apoptosis. If the DNA can be repaired, p53 activates other genes to fix the damage. If the DNA cannot be repaired, this protein prevents the cell from dividing and signals it to undergo apoptosis. By stopping cells with mutated or damaged DNA from dividing, functional p53 helps prevent the development of tumors. Because of this function, p53 is nicknamed the "guardian of the genome" [7].
Somatic mutations in the TP53 gene occur in almost half of all ovarian cancers. TP53 encodes for the protein called p53, a tumor suppressor that helps keep cells from growing and dividing uncontrollably. Most of these mutations change single amino acids in the p53 protein, which reduces or eliminates the protein's tumor suppressor function. Because the altered protein is less able to regulate cell growth and division, a cancerous tumor can develop [6].
The p53 protein is located in the nucleus and binds directly to DNA. When the DNA in a cell becomes damaged by agents such as toxic chemicals, radiation, or ultraviolet (UV) rays from sunlight, p53 plays a critical role in determining whether the DNA will be repaired or whether the damaged cell will undergo apoptosis. If the DNA can be repaired, p53 activates other genes to fix the damage. If the DNA cannot be repaired, this protein prevents the cell from dividing and signals it to undergo apoptosis. By stopping cells with mutated or damaged DNA from dividing, functional p53 helps prevent the development of tumors. Because of this function, p53 is nicknamed the "guardian of the genome" [7].
Resources:
Sources:
[1] American Cancer Society. What Is Ovarian Cancer? Retrieved January 31, 2017. https://www.cancer.org/cancer/ovarian-cancer/about/what-is-ovarian-cancer.html
[2] National Ovarian Cancer Coalition. Types & Stages of Ovarian Cancer. Retrieved January 31, 2017. http://ovarian.org/about-ovarian-cancer/what-is-ovarian-cancer/types-a-stages
[3] Ozols, R. F., Bookman, M. A., Connolly, D. C., Daly, M. B., Godwin, A. K., Schilder, R. J., ... & Hamilton, T. C. (2004). Focus on epithelial ovarian cancer. Cancer cell, 5(1), 19-24.
[4] Mayo Clinic. Ovarian Cancer Symptoms. (2014). Retrieved January 31, 2017. http://www.mayoclinic.org/diseases-conditions/ovarian-cancer/basics/symptoms/con-20028096
[5] Mayo Clinic. Ovarian Cancer Treatment and Drugs. (2014). Retrieved January 31, 2017.http://www.mayoclinic.org/diseases-conditions/ovarian-cancer/basics/treatment/con-20028096
[6] Genetics Home Reference. Ovarian Cancer. Retrieved January 31, 2017. https://ghr.nlm.nih.gov/condition/ovarian-cancer#genes
[7] Genetics Home Reference. TP53 gene. Retrieved January 31, 2017. https://ghr.nlm.nih.gov/gene/TP53#
[1] American Cancer Society. What Is Ovarian Cancer? Retrieved January 31, 2017. https://www.cancer.org/cancer/ovarian-cancer/about/what-is-ovarian-cancer.html
[2] National Ovarian Cancer Coalition. Types & Stages of Ovarian Cancer. Retrieved January 31, 2017. http://ovarian.org/about-ovarian-cancer/what-is-ovarian-cancer/types-a-stages
[3] Ozols, R. F., Bookman, M. A., Connolly, D. C., Daly, M. B., Godwin, A. K., Schilder, R. J., ... & Hamilton, T. C. (2004). Focus on epithelial ovarian cancer. Cancer cell, 5(1), 19-24.
[4] Mayo Clinic. Ovarian Cancer Symptoms. (2014). Retrieved January 31, 2017. http://www.mayoclinic.org/diseases-conditions/ovarian-cancer/basics/symptoms/con-20028096
[5] Mayo Clinic. Ovarian Cancer Treatment and Drugs. (2014). Retrieved January 31, 2017.http://www.mayoclinic.org/diseases-conditions/ovarian-cancer/basics/treatment/con-20028096
[6] Genetics Home Reference. Ovarian Cancer. Retrieved January 31, 2017. https://ghr.nlm.nih.gov/condition/ovarian-cancer#genes
[7] Genetics Home Reference. TP53 gene. Retrieved January 31, 2017. https://ghr.nlm.nih.gov/gene/TP53#