Researchers map the genome of testicular cancer

June 12, 2018 by Laura Oleniacz, UNC Lineberger Comprehensive Cancer Center
UNC Lineberger's Katherine Hoadley, PhD. Credit: UNC Lineberger Comprehensive Cancer Center

Testicular germ cell cancer, a disease that is rare but growing in incidence in men in the United States, is considered to be among the most curable of solid tumors. Now researchers from the University of North Carolina Lineberger Comprehensive Cancer Center and a consortium of institutions have discovered the genetic and genomic characteristics that define the disease.

In a collaborative effort of The Cancer Genome Atlas Research Network, which is a multi-institution effort to map the genetic and genomic changes in , researchers analyzed 137 testicular for potential mutations and other molecular changes. They identified molecular features of testicular germ cell cancers that could inform future efforts to improve treatment decisions, and help monitor patients to see if their cancer has come back. Their findings were published in Cell Reports.

"We now have a better understanding of the molecular characteristics of the histological subtypes of testicular germ cell cancers," said UNC Lineberger's Katherine Hoadley, Ph.D., assistant professor in the UNC School of Medicine Department of Genetics, and the study's corresponding author. "There is a strong epigenetic component to testicular cancer tumorigenesis."

Testicular cancer is a rare cancer in the United States, with about 9,310 new cases and 400 deaths occurring each year, according to the American Cancer Society. The disease is considered to be among the most curable solid tumors, with 95 percent of patients living five years, according to the National Cancer Institute. Researchers say research is needed to help stratify patients by risk to avoid over treatment and potential side effects, as well as to better monitor them after treatment.

"Risk stratification, currently based on clinical factors and serum markers, is critically important in a disease with issues related to both under-and-over treatment," said UNC Lineberger's Matthew Milowsky, MD, co-director of the UNC Lineberger Urologic Oncology Program, and professor in the UNC School of Medicine Division of Hematology/Oncology. "The great majority of patients with good-risk, advanced testicular germ cell tumors are cured, however, both early and late treatment-related complications remain problematic."

The researchers found few genetic mutations across the testicular germ cell cancers they analyzed. If they did find recurrent mutations in the tumors, it was only in one type of testicular cancer known as seminoma, and occurred in only one of three genes: KIT, KRAS and NRAS. More commonly, the tumors showed signs of duplicated DNA, or aneuploidy, and defects in their DNA methylation, which dictates whether genes are "on" or "off."

In some cases of the seminomas, they identified mutations in a gene called KIT, which is known to be an important gene in testes development. This subset of seminomas also lacked the methylation marks on their DNA. This lack of marks led researchers to believe that these cancer are locked in an early developmental state.

Hoadley and her colleagues also used their findings to identify markers that could potentially be used to monitor patients to see if their cancer had come back. They discovered that certain microRNAs were expressed differently in the different types of testicular germ cell tumors, and could potentially be explored as markers of low risk, or cancer recurrence.

"We found microRNAS that could be used to detect the different types of , and this potentially could be developed into a minimally invasive serum blood test to determine if their cancer has come back," Hoadley said. "We think that could be important for future screening."

Milowsky said while serum tumor markers are being used in clinic to stratify risk for testicular germ cell tumors, this study could point to additional markers that could boost these efforts.

In addition, he said the study's findings could to lead to possible novel targets for therapeutic strategies to reprogram the epigenome, or increase the immune system's response to the tumors.

"Advanced germ cell tumor treatment remains a success story in the field of oncology, however continued research aimed at increasing cure rates in patient with intermediate and poor-risk disease, and decreasing treatment related morbidity are desperately needed," he said.

Explore further: Study sheds new light on inherited testicular cancer risk

Related Stories

Study sheds new light on inherited testicular cancer risk

June 12, 2017
An analysis of data from five major studies of testicular cancer has identified new genetic locations that could be susceptible to inherited testicular germ cell tumors. The findings, which researchers call a success story ...

Study reveals why testicular cancer is so responsive to chemo

November 14, 2017
Cornell researchers have taken a major step toward answering a key question in cancer research: Why is testicular cancer so responsive to chemotherapy, even after it metastasizes?

Blood mutations could contaminate genetic analyses of tumors

June 5, 2018
Genetic mutations in blood cells that have made their way into tumors could be red herrings that mislead physicians looking for genetic changes in tumors that are helping to drive the cancer. This finding is significant because ...

Scientists identify unique genomic features in testicular cancer

November 30, 2016
Researchers led by scientists at Dana-Farber Cancer Institute say they have identified unique genomic changes that may be integral to testicular cancer development and explain why the great majority are highly curable with ...

Genomic analysis of thousands of tumors supports new cancer classification

April 5, 2018
University of North Carolina Lineberger Comprehensive Cancer Center researchers are reporting the concluding findings from a major analysis of nearly 10,000 different tumor samples that focused on identifying similarities ...

Recommended for you

Research team discovers drug compound that stops cancer cells from spreading

June 22, 2018
Fighting cancer means killing cancer cells. However, oncologists know that it's also important to halt the movement of cancer cells before they spread throughout the body. New research, published today in the journal Nature ...

Dying cancer cells make remaining glioblastoma cells more aggressive and therapy-resistant

June 21, 2018
A surprising form of cell-to-cell communication in glioblastoma promotes global changes in recipient cells, including aggressiveness, motility, and resistance to radiation or chemotherapy.

Existing treatment could be used for common 'untreatable' form of lung cancer

June 21, 2018
A cancer treatment already approved for use in certain types of cancer has been found to block cell growth in a common form of lung cancer for which there is currently no specific treatment available.

Novel therapy makes oxidative stress deadly to cancer

June 21, 2018
Oxidative stress can help tumors thrive, but one way novel cancer treatments work is by pushing levels to the point where it instead helps them die, scientists report.

Higher body fat linked to lower breast cancer risk in younger women

June 21, 2018
While obesity has been shown to increase breast cancer risk in postmenopausal women, a large-scale study co-led by a University of North Carolina Lineberger Comprehensive Cancer Center researcher found the opposite is true ...

Researchers uncover new target to stop cancer growth

June 21, 2018
Researchers at the University of Wisconsin-Madison have discovered that a protein called Munc13-4 helps cancer cells secrete large numbers of exosomes—tiny, membrane-bound packages containing proteins and RNAs that stimulate ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.