Accepted Abstracts: J Cancer Sci Ther
Intra-tumor heterogeneity can confound mutational status in oncodriver genes and challenge targeted cancer therapy strategies. Ultra-deep sequencing can detect low-frequency and expanded clonal mutations in primary tumors to better inform treatment decisions. KRAS coding exons in 61 treatment naive colorectal cancer (CRC) tumors were sequenced, with KRAS, EGFR, ALK, and MET in lung tumors from 3 Chinese non-small cell lung cancer (NSCLC) patients. Forty-two percent of CRC patients (28/61) harbored mutations in the KRAS active domain, eleven of which (18%) not detected by Sanger sequencing; 5/11 had frequencies <10%, and 12 patients harbored >1 mutation. Low frequency KRAS active (G12R) and EGFR kinase domain mutations (G719A) were identified in one NSCLC patient. Multiple low frequency mutations in KRAS, EGFR, and MET and ALK gene copy number increases were found in a second NSCLC patient. A third NSCLC patient showed EML4-ALK fusion with ALK, EGFR, and MET mutations. Within the same patient, multiple low frequency mutations occurred within a gene. A complex pattern of intrinsic low frequency driver mutations in well-known tumor oncogenes may exist prior to treatment, resulting in resistance to targeted therapies. Ultra-deep sequencing can characterize intra-tumor heterogeneity and identify such mutations to ultimately impact treatment decisions.
Yihong Yao is director and head of Pharmacogenomics and Bioinformatics Group at MedImmune, LLC. The focus of Dr. Yao?s group is the utilization of cutting edge genomics and genetics approaches to develop pharmacodynamics and predictive diagnostic markers to understand disease linkage and to identify the right patients that might respond (or not respond) to therapeutic interventions. The other areas of interest in Yao?s group include: to unveil potential key drivers in cancer, respiratory and inflammatory diseases, and to understand the role of miRNAs in disease pathogenesis. He received a bachelor?s degree in Biochemistry from Fu Dan University in 1988. He received a master?s degree in Bioinformatics from Boston University. He completed his doctorate in Biochemistry and Biophysics from the University of Kansas in Lawrence, Kansas. He conducted his postdoctoral research at Johns Hopkins Medical School in Baltimore, Maryland. He has authored over 50 peer-reviewed publications, edited two books and has over 15 patents.