UCSD. US: A team that includes scores of researchers from across the country
representing dozens of universities and medical institutions has
produced the most comprehensive integrative analysis yet of head and
neck squamous cell carcinomas (HNSCCs), a particularly malignant and
deadly type of tumor that accounts for roughly 3 percent of all cancers
in the United States.
The study, published in today’s issue of Nature, is the
product of The Cancer Genome Atlas (TCGA), a federally funded project to
identify and catalog errors in DNA that cause cells to grow
uncontrollably, resulting in at least 200 forms of cancer and many more
subtypes.
Scott M. Lippman, MD, director of the UC San Diego Moores Cancer
Center, and Ezra Cohen, MD, professor and associate director for
translational science at Moores Cancer Center, are members of the
network.
The vast majority of head and neck cancers begin in the squamous
cells that line the moist surfaces of the mouth, throat, larynx
(voicebox), nasal cavities and salivary glands. Symptoms include lumps
that do not disappear, a persistent sore throat, difficulty swallowing
or a change in voice.
Men are more than twice as likely to develop a HNSCC as women. An
estimated 52,000 Americans are diagnosed each year. Worldwide, HNSCCs
affect more than 600,000 patients per year. Alcohol and tobacco use are
considered the two most important risk factors. Smoking is implicated in
the rise of HNSCCs in developing countries; the role of human
papillomavirus (HPV) has emerged as an important risk factor affecting
non-smokers.
HNSCCs are deadly. Despite surgery, radiation and chemotherapy,
roughly half of all patients die of the disease, usually within two
years of initial diagnosis. Except for HPV status, investigations of
various molecular and clinical risk factors have produced limited
clinical benefit.
Past genome-wide profiling of HNSCC cases has been limited in scope
and detail. Researchers with TCGA sought to create a much more
comprehensive picture of molecular alterations associated with the
disease, one that could help direct future treatments.
“Treatment at a comprehensive cancer center would offer potential
advantages, including the ability to detect molecular alteration with
accuracy and availability of novel therapies in clinical trials that can
be personalized to a person’s cancer but not yet approved,” said Cohen.
The scientists profiled 279 patients with HNSCCs (with the ultimate
goal of characterizing 500 patients with tumors). They found that
HPV-associated tumors were dominated by specific mutations and molecular
alterations that differed from those linked to smoking-related HNSCCs.
Other subgroups of tumors were connected to other specific mutations or
losses of cellular function.
The findings have clinical import. In most of the HNSCCs studied, the
researchers identified therapeutic candidate alterations. That is, by
correcting targeted mutations, they said it might be possible to improve
treatments of diverse HNSCCs or possibly prevent them altogether.
“The next steps are to understand more comprehensively which
molecular alterations affect prognosis,” said Cohen, “and more
importantly, how to best treat patients whose tumors harbor these
mutations. These are challenges currently being addressed at Moores
Cancer Center.”
Co-authors are all members or affiliates of The Cancer Genome Atlas.