JI Program: GI & Liver
Esophageal cancers (EC), particularly esophageal squamous cell carcinoma (ESCC), present significant medical and scientific challenges. EC is the sixth most frequent cancer in women, with China accounting for ~50% of EC cases worldwide. Many parts of northern China have some of the highest ESCC incidence levels in the world, yet the genetic and environmental factors underlying such remarkable geographic variation are currently unknown. ESCC is difficult to detect at an early stage, and difficult to treat after diagnosis. Currently, we do not fully understand the major ESCC subtypes in different populations, nor do we understand the patterns of growth, migration, and treatment response among different cells within a tumor. This lack of knowledge impedes effective prevention, accurate diagnosis, personalized treatment, and development of novel drugs. Using a uniquely powerful clinical resource developed at PKUHSC, high-throughput genomic profiling capabilities, and the strong statistical analysis expertise at Michigan Medicine, this collaboration proposed to characterize intratumoral heterogeneity by comparing genomic alterations in different sectors of the same tumor, and contrasting them with surrounding normal tissues as well as the metastatic tumors in nearby lymph nodes. The results will reveal major genes and pathways affected in each patient; an importantly, the regional variation will be analyzed to shed light on the temporal progression of key tumorigenic events, from normal tissue to primary tumor, and to metastasis. Elucidating the somatic mutation sources in ESCC will also help resolve the long-standing controversies regarding the epidemiological factors contributing to ESCC. This study will harness complementary strengths from our two institutions, and is expected to generate new mechanistic insights into within-tumor evolution and genomic diversity of ESCC.
- Two PKUHSC PhD students received extensive training at Michigan Medicine mentored by Dr. Li.
- 146 samples with high-density SNP genotyping and exome sequencing were analyzed and led to numerous publications.
- Yuan W, Liu Z, Lei W, Sun L,... Li JZ, Yang K ( June 27, 2017). Mutation landscape and intra-tumor heterogeneity of two MANECs of the esophagus revealed by multi-region sequencing. Oncotarget.
- Li J, Yan S, Liu Z, … Ke Y. Multiregional sequencing reveal genomic alterations and clonal dynamics in primary malignant melanoma of the esophagus. Cancer Research. 2018;78(2):338-347