Researchers have discovered a link between copy number alteration (CNA) and increased recurrence across multiple types of cancer. Their findings, published in eLife yesterday, suggest the percentage of a tumor's genome with alterations in copy number is associated with mortality in a range of cancers.
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 at Memorial Sloan Kettering Cancer Center. "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 prostate cancer, 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. This group consisted of patients with localized 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.