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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Center for Advancing Translational Sciences (NCATS)
Type
Linked Specialized Center Cooperative Agreement (UL1)
Project #
3UL1TR000004-07S1
Application #
8291650
Study Section
Special Emphasis Panel (ZRR1-CR-3 (01))
Program Officer
Wilde, David B
Project Start
2012-08-01
Project End
2013-06-30
Budget Start
2012-08-01
Budget End
2013-06-30
Support Year
7
Fiscal Year
2012
Total Cost
$492,690
Indirect Cost
$148,619
Name
University of California San Francisco
Department
Neurology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Durack, Juliana; Kimes, Nikole E; Lin, Din L et al. (2018) Delayed gut microbiota development in high-risk for asthma infants is temporarily modifiable by Lactobacillus supplementation. Nat Commun 9:707
Gradissimo, Ana; Lam, Jessica; Attonito, John D et al. (2018) Methylation of High-Risk Human Papillomavirus Genomes Are Associated with Cervical Precancer in HIV-Positive Women. Cancer Epidemiol Biomarkers Prev 27:1407-1415
Chorba, John S; Galvan, Adri M; Shokat, Kevan M (2018) A High-Throughput Luciferase Assay to Evaluate Proteolysis of the Single-Turnover Protease PCSK9. J Vis Exp :
Yanik, Elizabeth L; Hernández-Ramírez, Raúl U; Qin, Li et al. (2018) Brief Report: Cutaneous Melanoma Risk Among People With HIV in the United States and Canada. J Acquir Immune Defic Syndr 78:499-504
Galárraga, Omar; Rana, Aadia; Rahman, Momotazur et al. (2018) The effect of unstable housing on HIV treatment biomarkers: An instrumental variables approach. Soc Sci Med 214:70-82
Elion, Richard A; Althoff, Keri N; Zhang, Jinbing et al. (2018) Recent Abacavir Use Increases Risk of Type 1 and Type 2 Myocardial Infarctions Among Adults With HIV. J Acquir Immune Defic Syndr 78:62-72
Wehner, M R; Dalma, N; Landefeld, C et al. (2018) Natural history of lesions suspicious for basal cell carcinoma in older adults in Ikaria, Greece. Br J Dermatol 179:767-768
Liakoni, Evangelia; Gugelmann, Hallam; Dempsey, Delia A et al. (2018) Butanediol conversion to gamma-hydroxybutyrate markedly reduced by the alcohol dehydrogenase blocker fomepizole. Clin Pharmacol Ther :
Schafer, Anne L; Kazakia, Galateia J; Vittinghoff, Eric et al. (2018) Effects of Gastric Bypass Surgery on Bone Mass and Microarchitecture Occur Early and Particularly Impact Postmenopausal Women. J Bone Miner Res 33:975-986
Kimura, Takayuki; Kobiyama, Kouji; Winkels, Holger et al. (2018) Regulatory CD4+ T Cells Recognize Major Histocompatibility Complex Class II Molecule-Restricted Peptide Epitopes of Apolipoprotein B. Circulation 138:1130-1143

Showing the most recent 10 out of 662 publications