Researchers have identified a genomic “fingerprint” that identifies which breast, ovarian, pancreatic, and gastric cancers are likely to respond to platinum therapy or PARP inhibitors, according to a study published in Nature Communications.

The discovery of this genomic fingerprint—called signature 3—may simultaneously refine personalized medicine for cancer patients while expanding the population of cancer patients treated, researchers predicted.In this study, researchers analyzed millions of somatic mutations from the cancer genomes of 10,250 patients using a large-scale computational screen across 36 different types of tumors, looking for the pattern of signature 3 in each sample.“Not only did we confirm the presence of signature 3 in a significant percentage of breast, ovarian, and pancreatic cancers, we also found this molecular fingerprint in approximately 10% of stomach cancers,” which was an unexpected finding, said principal investigator Ludmil Alexandrov, PhD, Oppenheimer Distinguished Postdoctoral Fellow at Los Alamos National Laboratory, in Los Alamos, NM.

He added, “Gastric cancer is the third-most common cause of cancer-related deaths worldwide, and we have potentially identified a new treatment methodology for some of these patients.”The researchers also quantified the occurrence of the signature 3 fingerprint in 30% of ovarian, 27% of breast, and 8% of pancreatic cancers—a higher percentage than originally thought. These data suggest that the presence of signature 3 could be used as a biomarker to guide targeted therapy for these cancers, the researchers said.

“This is an extremely exciting finding which shows the importance of genomic sequencing for personalized healthcare in the future,” said the study’s corresponding author Michael Stratton, PhD, Director of the Wellcome Trust Sanger Institute, in Hinxton, England. “In years to come, routine genomic analysis of cancers could show which have the signature 3 fingerprint, and inform and transform treatment of thousands of patients with these specific breast, ovarian, pancreatic, and gastric cancers.”Previous studies have shown that pancreatic cancers with signature 3 are complete responders to platinum therapy. Similarly, clinicians employ platinum therapy or PARP inhibitor drugs for breast and ovarian cancer patients who have mutations in their BRCA1 and BRCA2 genes.This new study reveals that these two genes are only part of the equation.

“While all the patients with BRCA1 and BRCA2 mutations show this signature 3 fingerprint, there are also many patients who have signature 3 but don’t have mutations in BRCA1 and BRCA2,” said Suet Yi Leung, MBBS, MD, Professor and Chair of Gastrointestinal Cancer Genetics and Genomics at the University of Hong Kong. “By focusing exclusively on those two genes, clinicians may be missing many cancer patients with the genomic signature 3 who could benefit from PARP inhibitor drugs or platinum therapy. Even just for breast cancer, you could potentially double the population size that could be treated with this therapy.”The researchers’ next step is to test these therapies in clinical trials to see if patients with cancers that have the signature 3 fingerprint really do respond as hoped to these treatments.

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