Oral cancer represents a significant portion of head and neck cancer. The mortality rate for oral cancers is high, largely due to the late stage of diagnosis. Prognosis is better for patients detected early, preferably in the premalignant stage. Unfortunately, it is difficult to predict the risk of progression for the earliest stages (i.e., low-grade dysplasias) based on clinical and histological appearance. The objective of the proposed study is to use genomics to discover novel genetic markers to differentiate progressing low-grade dysplastic lesions from morphologically indistinguishable non-progressing low-grade lesions. ? The unique combination of clinical resources and genomics capacity in Vancouver enables the implementation of such a search for predictive markers. A centralized Oral Biopsy Service in British Columbia provides archival specimens with known outcome to support a retrospective identification of genetic alterations for use as candidate markers. A newly developed whole genome bacterial artificial chromosome array (uniquely containing the human genome in greater than 32,000 DNA segments) facilitates genome-wide profiling of minute specimens. Finally, an ongoing prospective study monitoring patients with low-grade dysplasia provides the infrastructure for validation of new genetic markers for progression. We will first use archival material to identify recurrent alterations in high-grade oral premalignant lesions (OPL) and tumors and select those that are frequent in progressing low-grade lesions but infrequent (or absent) in non-progressing lesions. Stepwise bioinformatics analysis will identify candidate progression markers from these alterations. The ability of these selected markers to predict disease outcome will then be tested in biopsies and exfoliated cell samples prospectively collected in the ongoing NIDCR-funded British Columbia Oral Cancer Prediction Longitudinal (OCPL) study. This information will be translated to new genetic tools, including a miniaturized OPL genomic DNA array and diagnostic FISH probes, which are optimized for analyzing minute lesion biopsies and exfoliated cells from lesion brushings. These tools will guide clinicians in the detection and management of early oral premalignant lesions. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE015965-02
Application #
6891360
Study Section
Special Emphasis Panel (ZDE1-PZ (15))
Program Officer
Shirazi, Yasaman
Project Start
2004-05-01
Project End
2008-03-31
Budget Start
2005-04-01
Budget End
2006-03-31
Support Year
2
Fiscal Year
2005
Total Cost
$270,000
Indirect Cost
Name
British Columbia Cancer Agency
Department
Type
DUNS #
209137736
City
Vancouver
State
BC
Country
Canada
Zip Code
V5 1-L3
Firmino, Natalie; Martinez, Victor D; Rowbotham, David A et al. (2016) HPV status is associated with altered PIWI-interacting RNA expression pattern in head and neck cancer. Oral Oncol 55:43-48
Martinez, Victor D; MacAulay, Calum E; Guillaud, Martial et al. (2014) Targeting of chemoprevention to high-risk potentially malignant oral lesions: challenges and opportunities. Oral Oncol 50:1123-30
Vercauteren, Suzanne M; Starczynowski, Daniel T; Sung, Sandy et al. (2012) T cells of patients with myelodysplastic syndrome are frequently derived from the malignant clone. Br J Haematol 156:409-12
Vucic, Emily A; Thu, Kelsie L; Robison, Keith et al. (2012) Translating cancer 'omics' to improved outcomes. Genome Res 22:188-95
Thu, Kelsie L; Pikor, Larissa A; Chari, Raj et al. (2011) Genetic disruption of KEAP1/CUL3 E3 ubiquitin ligase complex components is a key mechanism of NF-kappaB pathway activation in lung cancer. J Thorac Oncol 6:1521-9
Gibb, Ewan A; Enfield, Katey S S; Stewart, Greg L et al. (2011) Long non-coding RNAs are expressed in oral mucosa and altered in oral premalignant lesions. Oral Oncol 47:1055-61
Vucic, Emily A; Thu, Kelsie L; Williams, Ariane C et al. (2010) Copy number variations in the human genome and strategies for analysis. Methods Mol Biol 628:103-17
Tsui, Ivy F L; Garnis, Cathie (2010) Integrative molecular characterization of head and neck cancer cell model genomes. Head Neck 32:1143-60
Garnis, Cathie; Chari, Raj; Buys, Timon P H et al. (2009) Genomic imbalances in precancerous tissues signal oral cancer risk. Mol Cancer 8:50
Tsui, Ivy F L; Poh, Catherine F; Garnis, Cathie et al. (2009) Multiple pathways in the FGF signaling network are frequently deregulated by gene amplification in oral dysplasias. Int J Cancer 125:2219-28

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