Detecting Colorectal Cancer with New DNA Sequencing Method

Researchers seek to improve diagnosis, support genetic counseling, and enhance medical management.

Genetic mutations in hereditary colorectal cancers may be detectable, according to findings published in the Journal of Molecular Diagnostics.

Researchers from Baylor College of Medicine developed a method for overcoming existing limitations in colorectal cancer testing in order to create a comprehensive approach for mutation detection of PMS2. PMS2, while not fully understood, is believed to play a role in colorectal cancer and Lynch syndrome onset. The strategy the scientists developed aimed to improve diagnosis, support appropriate genetic counseling, and aid medical management.

The majority of Lynch syndrome cases stem from heterozygous germline mutations in the DNA mismatched repair genes MLH1 and MSH2, the authors explained in a press release. However, the current DNA sequencing detection methods are not advanced enough; these methods miss at least 16% of DNA because the mutation can occur in the PMS2 gene.

The researchers believe that this test can enhance accuracy and reduce waiting time for testing. They said patients who may have Lynch syndrome — the first step in about 3% of total colorectal cancers – and their family members can especially benefit from this diagnostic work. Close blood relatives of patients with Lynch syndrome can have up to 50% chance of inheritance, the authors noted.

The three part strategy includes combining targeted capture next generation sequencing (NGS), multiplex ligation dependent probe amplification, and long range PCR followed by NGS to simultaneously detect point mutations and copy number changes of the PMS2 gene, the statement continued.

“The results from three methods serve as cross validation for enhanced accuracy and reduced turnaround time,” added co-investigator Victor Wei Zhang, MD, PhD, Department of Molecular and Human Genetics, Baylor College of Medicine.

The researchers identified deletions in the coding region of the gene, duplications on two chromosomes, and a nonsense mutation. The method provided the scientists with a new tool for reliable molecular analysis of any genes, which contained multiple copies of sequences previously known as predecessors to Lynch syndrome, especially when the PMS2 gene was suspected to be defective.

The authors noted that even though Lynch syndrome patients only make up about 2 to 4% of all colorectal cancer cases, it is important to identify these patients because their relatives are at such a high risk for inheriting the condition. Once receiving a Lynch syndrome diagnosis, those patients who had not developed cancer could be offered regular colonoscopies and other surveillance testing for colorectal, endometrial, or other cancers.