The first comprehensive studies of genetic variation in head and neck squamous cell cancers have uncovered mutations that may help refine treatment for patients with the disease, according to researchers at The University of Texas MD Anderson Cancer Center.
The researchers found that the tumor-suppressing gene TP53 was mutated in 47 percent of the tumors, by far the most commonly affected gene. So far, attempts to restore normal expression of the p53 protein, and expression of other impaired tumor-suppressors, have largely been unsuccessful.
"However, the finding from an unbiased approach that p53 mutation is the most common genetic abnormality in head and neck tumors indicates that we have to keep working with p53 to determine how it can be best used as a biomarker and/or therapeutic target," Myers said.
Next most common was NOTCH1, which was altered in 15 percent of tumor samples. Previously found to be an oncogene in leukemia, the team's findings pointed to a tumor-suppressive role for NOTCH1 in head and neck cancer. The researchers are following up to sort out the gene's role.
"NOTCH1 plays a dual role in biology, maintaining stem cells in some tissues or causing them to terminally differentiate in other tissues. This might explain why it could be an oncogene in one context or a tumor-suppressor in another," said Mitchell Frederick, Ph.D., assistant professor in Head and Neck Surgery and co-lead author of the paper.
Newer, targeted cancer therapies typically aim to shut down expression of oncogenes, mutated or dysregulated genes that fuel cancer growth and survival. PI3K (6 percent of tumors) and HRAS (4 percent) were the most commonly mutated oncogenes identified by the two groups.
The team also found infrequent but significant alterations in the tumor-suppressors CDKN2A (9 percent) and FBXW7 (5 percent).