Ying Ni, PhD

Uncovering the complex biology behind inherited cancers to better predict risk and discover new therapeutic strategies for patients.

Impact

Genetics are a major contributor to heritable breast cancer, but not all patients with mutated genes will develop the disease. For those who do develop cancer, scientists remain unsure as to why, and this hampers the design of effective predictive tests, prevention strategies, and therapies. BRCA mutations are the most well-known inherited mutations for breast cancer, but there are many more. A pioneer in the field of cancer genomics, the late Dr. Charis Eng was well recognized for her work with inherited mutations in the gene PTEN. Her team identified PTEN as a tumor suppressor that prevents healthy cells from becoming cancerous. Further, when PTEN is altered, its tumor-blocking functions can be lost. The importance of PTEN is underscored in the familial cancer disorder PTEN Hamartoma Syndrome (PHTS). These individuals inherit mutations in PTEN and have an 85 percent risk of developing breast and other cancers. Dr. Ni, a long-term collaborator of Dr. Eng’s, continues her research to explore what additional factors are required to tip the scales and initiate cancer in individuals with PHTS, which could also inform our understanding of how cancer forms in other heritable breast cancers.

Progress Thus Far

Several biological factors could induce cancer in individuals with PTEN mutations, including additional inherited genetic alterations; spontaneous mutations that develop during a patient’s lifetime; and systemic, non-genetic, changes in the body (e.g., changes in metabolism or immunity). Dr. Eng led the investigations to further characterize the genetic makeup of PHTS cancers and identify mutations that may contribute to cancer development. To accomplish this, Drs. Eng, Ni and their colleagues analyzed the DNA of 600 patients with PHTS and their family members. Ultimately, they did find several genetic alterations that are associated with cancer, which require further study. In addition, they assessed breast tumor tissue from this patient cohort to show that their cancers are genetically and molecularly different from non-PHTS breast cancers. In the last year, they expanded the analysis to include examination of RNA sequence data.

What’s Next

To characterize the potential genetic and metabolic factors that can contribute to breast cancer risk in patients with PHTS, the team will continue to analyze the RNA sequence data they have collected. The team will build on Dr. Eng’s groundbreaking body of work on the PTEN gene and pursue promising results that identified cancer-specific metabolites. Dr. Ni and her colleagues will explore whether these metabolites could serve as biomarkers of cancer risk in PHTS. The team hopes to leverage these results and bring us closer to more precisely stratifying patients according to ‘real life’ cancer probabilities