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Biomarker Identified for Head and Neck Cancers

By Labmedica International staff writers
Posted on 28 Aug 2014
Sequenom\'s MassARRAY Analyzer 4 mass spectrometry system
The MassARRAY Analyzer 4 mass spectrometry system (Photo courtesy of SEQUENOM)
Evidence has been found suggesting that the deleterious health effects of a mutated gene may in large part be due to other genetic abnormalities, at least in head and neck squamous cell carcinoma (HNSCC).

The high mortality rates among head and neck cancer patients tend to occur only when mutations in the tumor suppressor gene coincide with missing segments of genetic material on the cancer genome's third chromosome.

Scientists at the University of California, San Diego (La Jolla, CA, USA) and their colleagues 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 US National Cancer Institute (Bethesda, MD, USA). All of the tumors were from patients younger than 85 years of age.

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 two 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. To patients with these cancers, the results mean that there may be therapeutic value in testing tumors for the two genetic identifiers, known as a tumor protein 53 (TP53) mutation and a 3p deletion (short for deletions of genetic information on the short arm "p" of the third chromosome).

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 coopt 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. HPV status was deduced from a polymerase chain reaction (PCR)-based MassARRAY Assay (Sequenom; San Diego, CA, USA) diagnostic provided on the data portal for cases where sequence-based data were not available. The team discovered that among human papilloma virus (HPV)-positive tumors, the most aggressive cancer cases were also highly linked to the presence of 3p deletions.

Quyen Nguyen, MD, PhD, associate professor of Otolaryngology-Head and Neck Surgery and a senior author of the study said, “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 is done with breast cancers. In the past, treatments have been based largely on the size and location of the tumor. Now, we know that some large tumors may respond to less aggressive treatment while some small tumors may need intensified treatment. This will have a huge impact for patients.” The study was published on August 3, 2014, in the journal Nature Genetics.

Related Links:

University of California, San Diego 
US National Cancer Institute
Sequenom




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