Common Genetic Mutation Overlooked in Two Cancer Types

Researchers have identified a genetic mutation, known as RNF43, in two cancer types: colorectal and endometrial.

Investigators from the Dana-Farber Cancer Institute and the Broad Institute of MIT and Harvard, suggest that this discovery ranks as one of the most common mutations, and is found in approximately 20% of colorectal and endometrial cancers.

The RNF43 mutated gene helps to control an important signaling pathway known as Wnt, which has been found in many forms of cancer. The RNF43 mutation could act as a biomarker, which may help identify patients with colorectal and endometrial cancer. This in turn may prompt researchers to develop targeted therapy drugs that target the Wnt pathway.

The newly discovered RNF43 mutation came from tumor samples obtained from colorectal cancer patients in two studies: Nurses’ Health Study (which has been following 121,000 healthy women since 1976), and the Health Professionals Follow-Up Study (which includes 52,000 men enrolled in 1986). Approximately 10 years ago, Dana-Farber researchers studied these gastrointestinal tumor samples obtained from the men and women in this study who developed cancer.

In the new study, 185 colorectal cancer specimens from this collection were analyzed using whole-exome DNA sequencing at the Broad Institute. It turns out that the RNF43 mutation was identified in 18.9% of the colorectal tumors. This result prompted researchers to re-analyze 222 colorectal cancer samples from The Cancer Genome Atlas (TCGA) project, and found the RNF43 mutation in 17.6% of the samples.

Other frequently mutated genes currently found in colorectal cancer include APC (75%), P53 (50%), and KRAS (40%).

With regard to endometrial cancer, researchers understood the abnormal Wnt signaling pathway associated with this type of cancer, so they re-analyzed 248 DNA endometrial cancer samples that had been previously published by TCGA scientists. They found a similar result--18.1% of the endometrial samples had the RNF43 mutation as well.

The interesting part of this discovery is that the RNF43 mutation plays such a significant role in colorectal and endometrial cancers, but has not been detected until now. Study authors believe the reason behind this is that the computer algorithms used by scientists of TCGA project may have misinterpreted the "signal" of the RNF43 mutation as an artifact of the sequencing process, and discarded it.

The study authors note that these kinds of comprehensive genomic cancer studies hold value, and should continue.