Tumor suppressor mutations alone don't explain deadly cancer
The study, published online
The link between the two had not been observed before because the mutations co-occur in about 70 percent of head and neck tumors and because full genetic fingerprints of large numbers of cancer tumors have become available only recently.
"These two genetic malfunctions are not two separate stab wounds to the body," said co-senior author
To patients with these cancers, the study's results mean that there may be therapeutic value in testing tumors for the two genetic identifiers, known as a TP53 mutation (short for tumor protein 53) and a 3p deletion (short for deletions of genetic information on the short arm "p" of the third chromosome).
TP53 plays a key role in regulating cell growth, detecting and fixing DNA, and directing cell apoptosis (death) if the DNA damage is irreparable. Because of this, the TP53 protein is sometimes called the "guardian of the genome."
The study's findings suggest that if both markers are present, treatment should be intensified. If only one mutation is present, treatment might be de-intensified because the TP53 mutation alone is less deadly than previously thought. The latter would have immediate benefits in reducing deaths caused by complications related to medical care.
"We are in the early stages of being able to personalize head and neck cancer treatments based on the tumor's actual biology, the same as what's done with breast cancers," said co-senior author
The study analyzed the complete genomic signatures of 250 cases of squamous cell head and neck cancer extracted from The Cancer Genome Atlas, a repository of sequenced cancer genomes for more than 20 different types of human cancers maintained by the
Of these, 179 had both mutations; 50 had one of the two mutations; and 22 had neither mutation. Comparisons with patient outcome data showed that half of patients with both mutations would likely die of cancer within 2 years, while 66 percent of patients with one or neither mutation would be expected to live five years or more. These survival statistics were independent of the patients' clinical cancer stage.
Besides causing cervical cancer, the human papilloma virus (HPV) is implicated in the growing epidemic of head and neck cancers in otherwise healthy adults. It is believed that the virus can co-opt the activity of TP53, affecting cells in much the same way as a TP53 mutation but without causing a mutation. For this reason, the analysis examined HPV-positive and HPV-negative tumors separately.
One of the study's more compelling discoveries is that among HPV-positive tumors, the most aggressive cancer cases were also highly linked to the presence of 3p deletions.
"Our findings raise fundamental questions about the role of TP53 in cancer and suggest that some of the deleterious health effects of TP53 mutations might actually be due to something else going on in the third chromosome," said lead author
Keywords for this news article include: Genetics, Oncology, Viral DNA, Chromosomes, Cell Nucleus, Tumor Suppression, Intranuclear Space, Cellular Structures, Intracellular Space, Head and Neck Cancer, Head and Neck Neoplasms,
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