NEW ORLEANS—Colorectal cancer cells are shed into the stool, providing a potential means for early detection using noninvasive approaches. A multi-center research effort has evaluated a set of three genetic markers that may indeed constitute a reliable genetic mutation analysis of stool, signifying cancer.
At the 92nd Annual Meeting of the American Association for Cancer Research, Jin Jen, MD, PhD, presented the report on behalf of investigators from Johns Hopkins, M.D. Anderson, Cornell, Howard Hughes Medical Institute, and the National Cancer Institute.
The study included 51 patients with colorectal cancers for whom paired stool and primary tumor samples were taken. Two complementary methods were developed to isolate stool DNA for robust PCR amplification of human gene fragments, and three genetic targets were used for mutation detection: K-RAS mutations, TP53 mutation (a common p53 mutation in colorectal cancer), and BAT26 deletion.
TP53 gene mutations were detected in the stool of 30 patients, and all of these mutations were confirmed in the primary tumors of these patients. Three of the 51 stool samples contained deletions at the BAT26 locus, and each of these gene alterations was also identified in the corresponding tumor specimen. K-RAS mutations were detected in 17 tumors but in only 8 stool samples; therefore, this component was considered less sensitive than TP53 and BAT26, said Dr. Jen, who recently moved to the NCI Laboratory of Population Genetics.
The 30 TP53 mutations were detected in all stages of cancer and at all sites in the colon. The three BAT26 cases included two Duke’s B tumors and one Duke’s C tumor. All were in the ascending colon. The eight K-RAS mutations in the stool included five Duke’s B and three Duke’s C cancers, and all were in the descending colon.
This study makes clear, Dr. Jen said, that the majority of colorectal cancers can be detected through alterations in the DNA purified from stool using these three genetic markers. The markers jointly detected cancer in 71% of patients with colorectal cancer and in 92% of patients whose tumors had an alteration.
The results lay the groundwork for large prospective studies to determine the sensitivity and specificity of the tests for screening asymptomatic patients.
