Overall burden of tumor genome changes can predict patient outcomes

September 4, 2018, eLife
cancer
Killer T cells surround a cancer cell. Credit: NIH

Researchers have discovered a link between certain changes in the genome of a tumor and increased chances of death across multiple types of cancer.

Their findings, published in eLife, suggest the percentage of a tumor's genome with alterations in copy number (or 'copy number alteration'; CNA) is associated with mortality in a range of cancers. CNA refers to the fact that a genome can contain different numbers of copies of the same gene (the copy number), which can be altered in , leading to the tumor having more or less copies of that same gene.

The research also shows that the percentage of these alterations in a tumor genome, known as the CNA burden, can be measured using a clinically approved sequencing technique, highlighting its potential to predict outcomes for cancer patients in a clinical setting.

"As clinical genomic analysis of tumors and tumor biopsies becomes more widespread, there is a growing need to understand the prognostic factors captured by genomic features including CNA," says lead author Haley Hieronymus, Senior Research Scientist in Charles Sawyers' lab at Memorial Sloan Kettering Cancer Center, US. "Many specific genes altered by CNA have been associated with cancer outcomes; however, the relationship between the outcome and the overall level of CNA harbored by a tumor is less well studied.

"We and others have previously found that, in primary , CNA burden and genome-wide CNA patterns are associated with both recurrence and the development of secondary malignant growths in other areas of the body, known as metastasis. But it is still unknown whether CNA burden is prognostic for prostate cancer survival, rather than recurrence and metastasis only, and whether the prognostic significance of tumor CNA burden extends to other cancer types. Our aim with the current study was to start addressing these questions."

To do this, Hieronymus and her team began by examining the genomic CNA landscape of prostate cancer in more than a hundred diagnostic biopsy specimens from a prostate cancer research group. This group consisted of patients with localised prostate cancer who were not treated with surgery or radiation within six months of diagnosis. "Our initial analysis revealed that tumor CNA burden is associated with cancer-specific death, independent of standard clinical predictors," Hieronymus explains.

The team next studied patient groups with primary breast, endometrial, kidney, thyroid and colorectal cancer, in addition to prostate cancer. In what they called an "unanticipated outcome" of their work, they discovered that tumor CNA burden is also significantly associated with disease-free and overall survival in these cancer types, with varying degrees of association.

Finally, they studied the clinical feasibility of measuring tumor CNA burden using the US Food and Drug Administration-cleared MSK-IMPACT next-generation sequencing assay. This technique confirmed that tumor CNA burden is associated with overall and disease-specific survival in both primary and metastatic tumors, and across different cancer types.

"Our results suggest that ongoing and future studies into the biology underlying the association of tumor CNA burden with multiple cancer outcomes will be a fruitful area for future investigation," concludes senior author and Howard Hughes Medical Institute Investigator Charles Sawyers, Chair of the Human Oncology and Pathogenesis Program at Memorial Sloan Kettering Cancer Center. "For now, we've shown how this burden can be measured using an approved sequencing assay, demonstrating the potential for incorporating CNA burden assessment into patient prognoses."

Explore further: Researchers track lethal prostate cancer to determine clonal origin

More information: Haley Hieronymus et al, Tumor copy number alteration burden is a pan-cancer prognostic factor associated with recurrence and death, eLife (2018). DOI: 10.7554/eLife.37294

Related Stories

Researchers track lethal prostate cancer to determine clonal origin

October 26, 2013
Prostate cancer has variable manifestations, ranging from relatively benign localized tumors to widespread life-threatening metastases. The origin of most prostate cancer metastases can be traced back to the primary tumor; ...

Novel sequencing approach seeks to detect cancer's genomic alterations

June 5, 2017
Findings from an early study evaluating a sophisticated new genomic-sequencing approach that analyzes cell-free DNA (cfDNA) in the blood of people with advanced cancer will help inform development of a future assay that could ...

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 ...

ONC201 may inhibit cancer stem cell self-renewals by altering their gene expression

August 2, 2017
ONC201 may inhibit cancer stem cell self-renewals by altering their gene expression, according to a study published August 2, 2017 in the open-access journal PLOS ONE by Varun Vijay Prabhu from Oncoceutics, Inc., USA and ...

FDG PET shows tumor DNA levels in blood are linked to NSCLC aggressiveness

November 6, 2017
Italian researches have demonstrated a better way of determining the aggressiveness of tumors in patients with advanced non-small cell lung cancer (NSCLC). In a study presented in the featured clinical investigation article ...

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

May 19, 2017
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 ...

Recommended for you

Some brain tumors may respond to immunotherapy, new study suggests

December 10, 2018
Immunotherapy has proved effective in treating a number of cancers, but brain tumors have remained stubbornly resistant. Now, a new study suggests that a slow-growing brain tumor arising in patients affected by neurofibromatosis ...

Study finds higher risk of breast cancer for women after giving birth

December 10, 2018
Younger women who have recently had a child may have a higher risk of breast cancer than their peers of the same age who do not have children, according to a large-scale analysis co-led by a University of North Carolina Lineberger ...

A code for reprogramming immune sentinels

December 10, 2018
For the first time, a research team at Lund University in Sweden has successfully reprogrammed mouse and human skin cells into immune cells called dendritic cells. The process is quick and effective, representing a pioneering ...

Researchers develop personalized medicine tool for inherited colorectal cancer syndrome

December 10, 2018
An international team of researchers led by Huntsman Cancer Institute (HCI) at the University of Utah (U of U) has developed, calibrated, and validated a novel tool for identifying the genetic changes in Lynch syndrome genes ...

Study shows key enzyme linked to therapy resistance in deadly lung cancer

December 10, 2018
Researchers at The University of Texas MD Anderson Cancer Center have identified a link between an enzyme tied to cancer formation and therapy resistance in patients with epidermal growth factor receptor (EGFR)-mutant non-small ...

Potential seen for tailoring treatment for acute myeloid leukemia

December 8, 2018
Advances in rapid screening of leukemia cells for drug susceptibility and resistance are bringing scientists closer to patient-tailored treatment for acute myeloid leukemia (AML).

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.