In the USA, more people die from oral squamous cell carcinoma (SCC) than melanoma, cervical or ovarian cancer and the incidence, particularly in young people, is increasing. Neck metastasis is the primary cause of death, but not all oral SCCs metastasize. Nevertheless, almost all oral SCC patients undergo neck dissection, surgery to remove the cervical (neck) lymph nodes, at the time of surgery to remove the primary tumor, because there are currently no clinical, pathologic or molecular markers that reliably discriminate oral SCCs that are at risk for metastasis and those that are not. Recent studies in our laboratories distinguished two oral SCC subtypes with distinct molecular signatures and metastatic rates. One subtype, the 3q8pq20 subtype, is characterized by the presence of one or more of the recurrent copy number aberrations, +3q, -8p, +8q and/or +20. The other subtype (non-3q8pq20) lacks these copy number alterations. The non-3q8pq20 subtype is associated with a low risk of metastasis (7%) compared to the 46% rate of metastasis in the 3q8pq20 subtype. This observation has been replicated in another independent retrospective study of oral SCC patients. Thus, DNA copy number alterations at one or more of these loci is a biomarker identifying a group of patients at low risk for metastasis, who could be spared the potentially unnecessary major surgery required for removal of the cervical lymph nodes. Here, we are proposing to translate these retrospective research findings into a test that could be used to identify patients at low risk of metastasis that would be suitable for use during the routine patient evaluation period prior to surgical removal of the tumor. We will develop a non-invasive assay for our DNA copy number signature (+3q, -8p, +8q, +20) that will use array CGH to measure copy number for chromosomes 3q, 8p, 8q and 20 and tumor genomic DNA obtained by brush biopsy of the patient's cancer prior to surgery. Our goal is to develop methods of procedure for sample collection (Aim 1) and copy number detection (Aim 2), as well as appropriately track and share information amongst the collaborators (Aim 3). This bench-to-bedside translational research will benefit from the CTSA resources and expertise of the collaborating CTSA-supported investigators and their institutions.
Neck metastasis is the primary determinant for prognosis of oral cancer patients. Here, recent research laboratory findings that identified a molecular signature for tumors with low risk of metastasis will be translated into a simple assay that would allow clinicians to confidently identify those patients, who would not require the additional major surgery to remove the neck lymph nodes.
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