Investigating KRAS/TP53 Co-Alterations in Pancreatic Cancer

Jashodeep Datta, MD, a surgical oncologist at Sylvester Comprehensive Cancer Center and assistant professor of Clinical at the University of Miami Miller School of Medicine, explains KRAS co-alteration in patients with pancreatic cancer.

Many pancreatic tumors have co-alterations in KRAS and TP53, explains Datta. The reason for these co-alterations is unknown, and oncologists also do not have a clear picture of how this effects the disease. These questions were explored preclinically and warrant further study.

TRANSCRIPT:

0:07 | We are very interested in understanding the chasm that exists between the genotype of pancreas cancer and the virulent phenotype of pancreas cancer. What makes it so hostile for patients? To do that we approach this from the genome of the pancreatic cancer cell, which is really the incipient event in pancreatic tumorigenesis. And what's very interesting about pancreas cancer is compared with all of the cancers, if you look across the Cancer Genome Atlas, pancreatic cancer is the number one cancer that has cooperated mutations of KRAS and TP53.

0:46 | We really want to understand if there is a biologic basis for that, and what are the downstream repercussions of that. The was really the basis of this study. The most important finding that really paved the way for the remainder of our study was our finding, using a cohort of 250 patients from the University of Miami, as well as validation in two independent datasets, one from the Cancer Genome Atlas, as well as one from an international molecularly annotated data set the ICGC, where we showed that patients who had quadrate mutations in KRAS and TP53 had worse survival and worse prognosis compared with patients who had mutations in either the carrier s gene alone. And they had may have other mutations, but not TP53, or TP53 mutations alone, but not KRAS. So, this really paved the foundation for the remainder of the study.