Researchers from Wake Forest Baptist Comprehensive Cancer Center (WFBCC), Winston-Salem, NC have made novel discoveries about the genomic signatures of cancers—including bladder cancer—in smokers and persons of African-American ancestry.
The recently published findings (Theranostics 2017; 7:2914-23) provide strong evidence that tobacco is a major cause of genomic instability and heterogeneity in cancer, help to explain racial/ethnic disparities in cancer outcomes, and have implications for designing targeted therapy with existing and investigational agents, said senior author Wei Zhang, PhD, Wake Forest School of Medicine.
In the study, tumor samples were analyzed from 431 patients with advanced, treatment-refractory cancer who are enrolled in the Wake Forest Precision Oncology Trial. The genomic profiling was done by a commercial laboratory (Foundation Medicine) using Next Generation Sequencing and included analyses of mutations, rearrangement, and copy number alterations for 415 cancer-related genes.
Consistent with previous reports, the results showed a significantly higher mutational load in tumors of current smokers compared with those of former and never smokers and a high mutational load in smoking-related types of tumors. Using a new method for analyzing tumor clonality (SciClone), the investigators also identified increased intratumoral clonal heterogeneity in the smoking-related tumors; ie, the tumors were comprised of multiple “subtumors” having differing mutational landscapes.
Analyses with patients stratified by race/ethnicity showed that compared with Caucasian patients, the African-American patients had a similar mutational landscape overall. The African-Americans, however, had a significantly higher rate of mutations in two key genes—the tumor suppressor gene TP53 and KMT2C, a chromatin remodeling gene—along with significant amplification of five other oncogenes.
The findings for most of the gene mutations related to smoking and race/ethnicity were validated using data from patients enrolled in The Cancer Genome Atlas, Dr. Zhang told Urology Times.