Sequencing prostate tumors from African-American men reveals a novel tumor suppressor gene

May 19, 2017 by Leah Eisenstadt, Broad Institute of MIT and Harvard
Micrograph showing prostatic acinar adenocarcinoma (the most common form of prostate cancer) Credit: Wikipedia

African-American men develop prostate cancer more often than other men, and it tends to be more deadly for this population. Some of the differences seem to be due to socioeconomic factors, but scientists wondered whether the disparities are also rooted in the tumor genome.

To explore whether racial disparities in incidence and prognosis stem from molecular and , a team of researchers at the Broad Institute of MIT and Harvard including Broad institute member Levi Garraway and postdoctoral researcher Franklin Huang gathered tumor samples from 102 African-American men with prostate cancer and analyzed their exomes. The work appears in Cancer Discovery.

After sequencing the exomes (protein-coding portions of the genome) from these tumors and validating their results in another 90 patients, they uncovered several mutations not recognized before in this setting. Interestingly, they found that the gene ERF, which had never been implicated in any particular cancer, was mutated in 5 percent of the men in the study. ERF is a member of the ETS family of transcription factors, and rearrangements in other ETS family genes have been found in prostate cancer and are thought to drive cancer by turning other genes on. The genetic misspellings they found in ERF, however, are so-called "loss-of-function" mutations that effectively remove the function of the gene, demonstrating that ERF is a novel prostate cancer tumor suppressor gene that normally acts to slow cancer growth.

When they examined existing data on prostate cancer samples from other cohorts, such as The Cancer Genome Atlas (TCGA) project which includes people of mostly European descent, they observed that the ERF gene was deleted in 3 percent of primary prostate cancers and mutated or deleted in 3-5 percent of lethal prostate cancers that had become resistant to androgen-depleting therapy. The alterations in the TCGA samples weren't significant enough on their own to implicate ERF, but in light of the findings in the new study, support a role for the mutant gene in driving prostate cancer.

The researchers also found differences in other , including amplifications (present in multiple copies) and deletions, but more work remains to fully explain the disparity in prostate cancer incidence and severity among patients of different ancestries. Because prostate cancer has a relatively low mutation rate compared to other cancers, many more samples may be needed. The scientists plan to look for genetic differences among larger groups of African-Americans, and to also study patients native to West Africa, a region in which African-Americans tend to have ancestry.

The success of this effort in uncovering subtle genomic differences and revealing a new gene demonstrates the power of including diverse populations in genetic analyses. Discoveries made from studying patients of diverse ethnic backgrounds can shed light on the underlying biology of this disease for all patients.

Explore further: Are men with a family history of prostate cancer eligible for active surveillance?

More information: Franklin W. Huang et al. Exome Sequencing of African-American Prostate Cancer Reveals Loss-of-FunctionMutations, Cancer Discovery (2017). DOI: 10.1158/2159-8290.CD-16-0960

Related Stories

Are men with a family history of prostate cancer eligible for active surveillance?

April 6, 2017
Active surveillance—careful monitoring to determine if or when a cancer warrants treatment—is an increasingly prevalent choice for prostate cancer, but it's unclear if the strategy is appropriate for men with a family ...

Researchers identify 'synthetic essentiality' as novel approach for locating cancer therapy targets

February 6, 2017
A new method has been found for identifying therapeutic targets in cancers lacking specific key tumor suppressor genes. The process, which located a genetic site for the most common form of prostate cancer, has potential ...

New oncogene linked to prostate cancer in African Americans may lead to better diagnostic tools

October 21, 2016
A team of scientists has identified MNX1 as a new oncogene - a gene than can cause cancer - that is more active in African American prostate cancer than in European American prostate cancer. The finding suggests that genetic ...

Research helps explain why androgen-deprivation therapy doesn't work for many prostate cancers

January 5, 2017
Metastatic prostate cancer, or prostate cancer that has spread to other organs, is incurable. In new research published in the journal Science, Roswell Park Cancer Institute scientists have identified two gatekeeper genes ...

Novel mutation may be linked to prostate cancer in African American men

February 23, 2017
Researchers have identified a novel mutation that may be associated with prostate cancer in African American men, according to a new study published in PLOS Computational Biology.

Genetic differences may cause higher rates of prostate cancer in African-American men

September 20, 2011
Genetic differences in prostate cells seem to be a root cause of the prostate cancer disparities between African-American men and white men, according to findings presented at the Fourth AACR Conference on The Science of ...

Recommended for you

Single blood test screens for eight cancer types

January 18, 2018
Johns Hopkins Kimmel Cancer Center researchers developed a single blood test that screens for eight common cancer types and helps identify the location of the cancer.

Researchers find a way to 'starve' cancer

January 18, 2018
Researchers at Vanderbilt University Medical Center (VUMC) have demonstrated for the first time that it is possible to starve a tumor and stop its growth with a newly discovered small compound that blocks uptake of the vital ...

The pill lowers ovarian cancer risk, even for smokers

January 18, 2018
(HealthDay)—It's known that use of the birth control pill is tied to lower odds for ovarian cancer, but new research shows the benefit extends to smokers or women who are obese.

These foods may up your odds for colon cancer

January 18, 2018
(HealthDay)—Chowing down on red meat, white bread and sugar-laden drinks might increase your long-term risk of colon cancer, a new study suggests.

How cancer metastasis happens: Researchers reveal a key mechanism

January 18, 2018
Cancer metastasis, the migration of cells from a primary tumor to form distant tumors in the body, can be triggered by a chronic leakage of DNA within tumor cells, according to a team led by Weill Cornell Medicine and Memorial ...

Modular gene enhancer promotes leukemia and regulates effectiveness of chemotherapy

January 18, 2018
Every day, billions of new blood cells are generated in the bone marrow. The gene Myc is known to play an important role in this process, and is also known to play a role in cancer. Scientists from the German Cancer Research ...

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.