Gastric Cancer: Gene Mutation Predictive of Response to Immunotherapy Interview with:

Wei Zhang, Ph.D. Hanes and Willis Family Professor in Cancer Director Cancer Genomics and Precision Oncology Wake Forest Baptist Comprehensive Cancer Center Winston-Salem, NC  27157-1082

Prof. Zhang

Wei Zhang, Ph.D.
Hanes and Willis Family Professor in Cancer
Cancer Genomics and Precision Oncology
Wake Forest Baptist Comprehensive Cancer Center
Winston-Salem, NC  27157-1082 What is the background for this study? What are the main findings?

Response: Gastric cancer is a leading cause of cancer-related death worldwide. Infection by the Helicobacter pylori is the major cause of gastric cancer, which accounts for more than 60% of cases. Despite progress in helicobacter pylori eradication and early cancer diagnosis, the five-year survival rate of gastric cancer remains less than 30%. Gastric cancer is one of the most common cancer types in Asia but the incidence for gastric cancer has seen a steadily increase in the United States in recent years.

Immunotherapy treatment has shown remarkable benefit for some cancer patients whereas others experience toxicities. It is important to identify markers that help oncologists decide which patient would benefit from this promising new treatment strategy. It has been suggested that gastric cancer that is positive for Epstein-Barr Virus is likely more responsive to immunotherapy but only about 10% of gastric cancer patients belong to this category. More potential markers are urgently needed for clinical practice.

There is accumulating evidence that high tumor mutation load, which means there are high numbers of gene mutations in the tumor, can provide a signal to activate immune response systems thus rendering tumors more sensitive to immunotherapy. What should readers take away from your report?

Response: In this study, a team of scientists consisted of bioinformatician (Dr. Xiangchun Li), epidemiologist (Kexin Chen), oncologist (Boris Pasche), and cancer biologist (Wei Zhang)performed systematic and comprehensive analyses of 437 gastric cancer samples from The Cancer Genome Atlas (TCGA) and 256 gastric cancer samples from an Asian cohort. The TCGA cohort was used as discovery set, while the Asian cohort was used as a validation set. Key findings include:

  • Mutation of a gene called MUC16 was observed in 22% and 38% of gastric cancer in Asian and TCGA cohort, respectively.
  • Mutation of MUC16 was associated with higher tumor mutation load.
  • Mutation of MUC16 was associated with survival outcomes in patients with gastric cancer.
  • Samples with MUC16 mutations exhibited upregulated signaling pathways related to immune system and antigen processing. What recommendations do you have for future research as a result of this work?

Response: These findings identified a potential new marker that may guide immunotherapy for up to a 38% of gastric cancer patients. Interestingly, MUC16 gene encodes a protein also known as CA125, which is a key blood marker for ovarian cancer. Future studies will examine the relationship between MUC16 gene mutation and CA125 blood level in gastric cancer.

Mucin gene family emerges as a clinically important group of genes. In another recent study published in Lancet Oncology last year by Wake Forest Comprehensive Cancer Center, we reported that mutations of several other MUC genes may contribute to better response to a metabolic targeting drug called CPI-613 in pancreatic cancer. We are very intrigued that MUC16 becomes another member of this gene family that may become genetic factor that affect therapeutic response in gastric cancer.  


Li X, Pasche B, Zhang W, Chen K. Association of MUC16 Mutation With Tumor Mutation Load and Outcomes in Patients With Gastric Cancer. JAMA Oncol. Published online August 09, 2018. doi:10.1001/jamaoncol.2018.2805

Aug 10, 2018 @ 12:24 pm

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