Advertisement

New Ultrasensitive Screening Method Can Detect Colon Cancer in Its Early Stages

Advertisement

Key Points

  • A new ultrasensitive screening method that detects genetic variations that initiate colon cancer could be used for noninvasive colon cancer screening.
  • The screening techniques, which use wild-type blocking polymerase chain reaction and high-resolution melting, can detect very low amounts of different types of cancer-initiating mutations in APC and KRAS genes in stool samples.
  • A multicenter study is needed to validate the sensitivity and specificity of the new screening method in comparison with standard screening methods for colon cancer such as colonoscopy.

A new ultrasensitive screening method that detects genetic variations that initiate colon cancer and can help in the detection of the cancer in its early stages could be used for noninvasive colon cancer screening, according to a study by Bettina Scholtka, PhD, Assistant Professor in the Department of Nutritional Toxicology at the University of Potsdam in Nuthetal, Germany, and colleagues. The screening method can spot a single cancer-specific gene variation among 10,000 times the amount of normal DNA, and is up to 5,000-fold more sensitive than other noninvasive screening methods. The study is reported in Cancer Prevention Research.

About 60% and 40% of patients with colorectal cancer have genetic variations in the genes APC and KRAS, respectively. Since these variations are also present in precancers, methods for detecting them can help spot colon cancers early.

The scientists used 80 human colon tissue samples representing cancers and precancers to detect genetic variations using a combination of two techniques. The first technique was locked nucleic acid–based, wild-type blocking (WTB) polymerase chain reaction, which suppressed normal DNA present in large quantities in the sample. The second technique was high-resolution melting (HRM), which enhanced the detection of genetic variations.

Early Cancers and Precancers Detectable in Stool Samples

The researchers were able to detect APC variations in 41 of the 80 tissue samples, and were also able to detect previously unknown variations in APC. Conversely, the routinely used technique called direct sequencing could detect variations in only 28 samples. The scientists then analyzed 22 stool samples from patients whose colon tissues had APC variations and 9 stool samples from patients whose colon tissues did not have APC variations as controls. They found APC variations in 21 out of 22 samples. The researchers also detected variations in the KRAS gene using 20 human colon tissue samples to show that the WTB-HRM method can be used to detect variations in genes other than APC.

“WTB-HRM is a new approach for ultrasensitive detection of cancer-initiating mutations. In this sense, it appears especially applicable for noninvasive detection of colon cancer precursors in body fluids with excess wild-type DNA like stool,” wrote the scientists.

“By using our technique for examining a selection of genes that become mutated during the process of colon cancer formation, it is possible to detect the very first stage of colon cancer and even precancers in a stool sample,” said Dr. Scholtka in a statement. “It will be possible to prevent cancer in many cases by removing the precancerous lesions after early detection.”

Dr. Scholtka also noted that a multicenter study is needed to validate the sensitivity and specificity of the new screening method in comparison with standard screening methods for colon cancer such as colonoscopy.

This study was supported by the Foundation for Pathobiochemistry and Molecular Diagnostics and the German Society for Clinical Chemistry and Laboratory Medicine.

The researchers reported no conflicts of interest.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


Advertisement

Advertisement




Advertisement