BU researchers identify mutational signatures and tumor activity in Chinese patients

(Boston)—Many different mutational signatures, or "fingerprints" of DNA damage have been identified across different tumor types which can provide a record of environmental exposure or clues about the etiology of carcinogenesis. Most of the mutational signature characterization has been performed using tumors from American and European populations due to the availability of sequencing data in these regions from large-scale atlases such as The Cancer Genome Atlas and the International Cancer Genome Consortium. While some unique mutational signatures have been identified in various Asian populations, mutational signatures and their activity in tumors from Chinese patients have not been well characterized across cancer types.

Researchers from Boston University Chobanian & Avedisian School of Medicine have now identified mutational signatures that are highly active in a large Chinese population. They found that the majority of the mutation-causing processes were similar between American and Chinese populations. However, they did find differences in what the mutational signature activities were correlated with.

“While cancer incidence and mortality can vary across regions and countries, the degree to which mutational signatures are similar or different between populations remains an open area of exploration, creating a major blind spot in our medical knowledge,” explains corresponding author Joshua D. Campbell, PhD, associate professor of medicine at the school.

The researchers analyzed publicly available mutation data from more than 2,000 tumors from 25 different cancer types. Using their own statistical methods from their software toolkit called "musicatk," they were able to identify what mutational signatures were present in the Chinese cohort and determine if the activity level of those signatures is correlated with important clinical or biological characteristics. 

While the researchers found that the majority of signature activities were not significantly different between the populations, they did observe lower levels of UV-associated mutations in a type of skin cancer called cutaneous melanoma in the Chinese cohort compared to the American cohort. In general, the prevalence of melanoma is 54 times lower in men and 60 times lower in women in China compared to the U.S. “Our findings corroborate and expand recent work showing that the number of UV-associated mutations in normal skin is lower in Asian populations compared to other populations despite Asian populations having higher levels of exposure to UV radiation,” says Campbell.

Aristolochic acid has been found in a Chinese herbal medicine and is known to cause some types of cancer or kidney failure. The authors are the first to report the presence of a mutational signature associated with aristolochic acid in a type of cancer called "soft tissue sarcoma" demonstrating that this carcinogen can cause additional types of cancer not previously recognized.

These findings appear online in the journal Cancer Research Communications, a journal of the American Association for Cancer Research.

Funding for this study was provided by the National Cancer Institute (NCI) Informatics Technology for Cancer Research (ITCR) 1U01CA253500 (J.D. Campbell and M. Yajima).