5 Apr 2018
The Cancer Genome Atlas — a joint effort between the National Cancer Institute (NCI), the National Human Genome Research Institute (NHGRI) and hundreds of scientists across six continents — and published this week in the prestigious journal Cancer Cell, researchers have a comprehensive resource for understanding the minute molecular changes that differentiate one type of GI cancer from another. [This week’s comprehensive analysis of gastrointestinal cancers was published along with 26 other studies detailing similar resources for many other cancer types. Read the announcement here.] “The better we are able to classify cancers based on their specific molecular characteristics, the better we can treat patients, both by developing new, more targeted therapies and by using this information to inform treatment decisions,” said Dr. Peter W. Laird, a professor at Van Andel Research Institute who was one of the leaders of the GI cancer study. “For GI cancers, our results confirmed some findings from smaller studies that focused on a single cancer type and also revealed differences between and within subtypes that have never before been described, which give us new opportunities to develop improved therapeutic strategies.” So, what exactly did they find? Why is it important? And what does it mean for the future of cancer research and treatment? Here are the top three takeaways: TAKEAWAY ONE GI adenocarcinomas can be divided into at least five subtypes based on molecular characteristics, a departure from traditional classification methods that use anatomic and tissue-specific features to differentiate between cancers. Historically, cancers have been categorized and named based on the organ or tissue in which they arose — for example, cancers that start in the esophagus have been called esophageal cancers and were believed to be similar to other cancers found in the esophagus, and so on. The findings urge a shift away from this view, based on new clarity into the incredibly complex web of factors that influence and differentiate one cancer from another. Rather than categorize by organ of origin, GI cancers should be classified by variations in genetic, epigenetic and molecular makeup, including:Scientists now have a powerful new resource for developing better treatments for common cancers of the esophagus, stomach, colon and rectum, collectively known as gastrointestinal (GI) adenocarcinomas. In all, these cancers claim more than 1.4 million lives annually across the globe. For more than 50 years, GI adenocarcinomas have largely defied therapeutic progress, stymying attempts to develop more effective medications and reduce the necessity of invasive surgeries. Now, thanks to landmark findings from
- The presence of Epstein-Barr virus (EBV), a common virus that has been linked to stomach cancer, and correlates to a specific type of epigenetic fingerprint.
- Microsatellite instability (MSI), which is caused by errors in the repair processes responsible for ensuring the genetic code is properly copied. These cancers may be particularly susceptible to immunotherapies.
- Hypermutated tumors with elevated single nucleotide variants (HM-SNV), which have an extreme number of genetic mutations brought on by problems with the polymerase enzyme that copies the DNA during replication. Often, these tumors have a better prognosis than other subtypes due to their increased mutational load, which can cause the body’s immune system to attack or, if a mutation occurs in a gene required for cell viability, can make it difficult for the cancer cell to survive at all.
- Chromosomal instability (CIN), which refers to problems in the 23 pairs of chromosomes that warehouse our DNA.
- Genome stability, or the ability of the genetic code to retain its integrity and pass on an accurate copy of our genetic instruction manual to the next generation of cells.