Genes that Drive or Delay Ovarian Cancer Identified
Sun, April 11, 2021

Genes that Drive or Delay Ovarian Cancer Identified

 

Some factors that make a woman more likely to develop epithelial ovarian cancer are known but much less is known about what exactly causes most ovarian cancers. There are limited studies about risk factors for stromal or germ cell tumors of the ovaries. Now, a team of scientists at the College of Veterinary Medicine pinpoints certain genes that drive or delay ovarian cancer.

HGSOC: the fifth leading cause of cancer-related deaths of women in the US

Published in journal by Cell Reports, their study highlights that high-grade serous ovarian carcinoma (HGSOC) is the fifth leading cause of cancer-related deaths of women in the US alone. The Cancer Genome Atlas Research Network has identified disease-associated mutations yet aside from mutations in the RB1 pathway or TP53 that are common in HGSOC, the contributions of these mutations remain unclear.

Senior author John Schimenti, who is also a professor of genetics in the Department of Biomedical Sciences, shared via Medical Xpress that their team has taken the massive collection of genomic mutation data mined on cancer genetics. Then, they tried to make a functional sense out of it. Cancer researchers have recognized that the disease is almost always caused by multiple genetic “hit,” meaning that tumor suppressor genes need both alleles to be inactivated either through epigenetic silencing or mutations. One mutation alone will turn a cell cancerous. Generally, at least two or three mutations are needed and it often involves different combinations of genes.

Schimenti said that adding complexity to cancer research is that once a single key genome-destabilizing mutation occurs, others will follow. The sequenced tumors will then result in a plethora of mutations, some are spinoffs while others are originators of cancer. It has been a longstanding issue in the field of cancer research. Scientists have been wondering what are the genetic passengers and the genetic drivers in the process.

Passenger and driver mutations in ovarian cancer

For their study, the team tests combinations of possible genetic suspects and analyze into parts which of the associated mutations were sparking ovarian cancer. So, they use the Cancer Genome Atlas, which is an international collaborative database that gathers the genetic information from tumor samples of patients and the mutated genes linked with them. The authors focused on the list of 20 genes that are known to mutate in ovarian cancer and used the CRISPR gene-editing technology – a genetic engineering technique by which the genome of living organisms may be modified.

The team then formed random combinations of these mutations from the ovary surface in cultured cells, including the epithelial stem cells and regular epithelial cells to know the cell type that is more susceptible to mutations. After that, they noted which of those combinations of mutations turned cells to be cancerous. Results show that ovarian surface stem cells, when hit with mutations, were more apt to become cancerous cells. The team likewise unexpectedly discovered the genes that had the opposite effect.

 

 

Significance of the study

Alexander Flesken-Nikitin, professor of pathology and director of the Cornell Stem Cell Program, shared that knowing which genes are necessary for initiating a highly aggressive form of ovarian cancer and which are the cells of origin can be “powerful information” not just in studying ovarian cancer but other types of cancer as well. This is because the cancer driver screening method they used can be applied in answering the same kinds of questions for cancers in other tissues and organs and cells.

Schimenti added that their findings can be particularly helpful for patients diagnosed with ovarian cancer, who have their tumors sequenced for genetic data and biopsied. Before their study, researchers may know which genes have mutated but they wouldn’t recognize what role these genes played. Now, they can tell which genes are important. Eventually, it will also help develop drugs that will target those mutated genes that are causing cancer.

Ovarian cancer statistics

According to the American Institute for Cancer Research, ovarian cancer is the eighth most commonly occurring cancer in women. In 2018, there were nearly 300,000 new cases of ovarian cancer and the top countries with the highest rates of ovarian cancer were Serbia (16.6 age-standardized rates per 100,000), Brunei (16.0), Belarus (15.4), Poland (14.7), and Latvia (14.3).

Meanwhile, the World Ovarian Cancer Coalition compared the survival statistics of ovarian cancer with those of breast, endometrial, and cervical cancer. The figures have been extracted from research that looked at 10, 5, and 1-year survival among the common types of cancer in people diagnosed in Wales and England for 40 years until 2011. The 5-year survival rate of breast cancer is 87%, endometrial 79%, cervical 67%, and ovarian 46%.

 

 

 

Annual cancer deaths, by cancer type

The annual cancer deaths, by cancer type measured as the total number of deaths in both sexes across all age categories, were also published by Our World in Data. In 2016, the global cancer deaths, by type were as follows: gallbladder cancer (101,834.00), Larynx cancer (111,044.00), other pharynx cancer (118,630.00), kidney cancer (131,800.00), ovarian cancer (165,041.00), lip and oral cavity cancer (176,489.00), bladder cancer (186,199.00), brain and nervous system cancer (227,039.00), non-Hodgkin lymphoma (239,580.00), and cervical cancer (247,160.00), among others.

In general, two-thirds of women diagnosed with ovarian cancer are 55 years old or older. Some common risk factors for ovarian cancer include genetics (family history, genetic mutations, Lynch syndrome and Peutz-Jeghers syndrome) and previous conditions (childbearing status, birth control use, and gynecologic surgery).

 

 

The American Cancer Society said there are several ways in which one can reduce their risk of developing the most common type of ovarian cancer, epithelial ovarian cancer. For example, the use of birth control pills decreases the risk of developing ovarian cancer for BRCA mutation carriers and average-risk women. Both hysterectomy and tubal ligation also reduce the chance of developing certain types of cancer although these operations should only be performed for the effect on ovarian cancer risk but valid medical reasons.

Schimenti and the team’s study is important as it will help pave the way to develop effective and safe methods to detect, diagnose, and ultimately cure ovarian cancer.