Abstract #LB-299: Identification of a copy number change as a prognostic factor for oral squamous cell carcinoma
Authors: Ken Miyaguchi, Kaoru Mogushi, Hiroshi Mizushima, Ken-ichiro Takahashi, Hiroaki Sato, Chieko Michikawa, Norihiko Okada, Narikazu Uzawa, Teruo Amagasa, Hiroshi Tanaka
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Introduction: Oral squamous cell carcinoma (OSCC) is the most common head and neck carcinoma and accounts for more than 270,000 cases worldwide every year. Prognosis of OSCC substantially depends on the presence of lymph node metastasis. This has been shown by that the cumulative survival rate in patients with lymph node metastasis, which was approximately 20% to 30% lower than patients without lymph node metastasis. Since genomic aberration is significantly related in various diseases including malignant neoplasm, a genome-wide study of copy number aberration (CNA) has been recently applied for cancer research using the high-density microarray to reveal the biological and clinical relation between CNA and various cancers. Our research is to find a novel prognostic factor in OSCC by investigating CNA. Materials and Methods: Genomic DNAs from 64 primary OSCC tissue samples collected at Tokyo Medical and Dental University (TMDU) Dental Hospital were analyzed by using Affymetrix Human Mapping 250K Sty array, which contains nearly 238,000 SNP probe sets. The CNA data was calculated based on the information of SNP probe intensities for each sample by Chromosome Copy Number Analysis Tool (CNAT) provided from the manufacturer. Subsequently, all of the CNA data was integrated along the chromosomes to identify the high frequent CNA regions. Fisher\#8217;s exact test was applied to reveal the correlation between various clinicopathological information and CNAs of about 26,000 genes referred from Entrez Gene database. Results: By the analyses of the CNA data with clinicopathological information, some genes were found with significant correlation ( p < 0.01), showing either copy number loss or gain/amplification in OSCC cases with late cervical lymph node metastasis. By selecting genes with the molecular characteristics, a few genes were identified as candidate genes that could be involved in the molecular mechanism of late cervical lymph node metastasis. Focused on one of the candidate genes, OCCN1 (laboratory internal gene ID) on chromosome 11 showed copy number gain/amplification in metastatic cases (5 of 16, 31.3%). CNA of OCCN1 was validated by FISH analysis and quantitative real-time PCR. As an additional statistical analysis for OCCN14, the Kaplan-Meier analysis showed the significant difference in the survival rates between two OSCC groups; a group with neutral copy number and a group with copy number gain/amplification (Log rank test, p < 0.0001). The overall survival rates of the group with copy number gain/amplification for OCCN1 were significantly lower than the other. Conclusion: CNA analyses identified some candidate genes involved in late cervical lymph node metastasis of OSCC. Although further functional analyses are necessary to verify the facts, the results suggest that some of these candidate genes including OCCN1 can be the prognostic factors for OSCC.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-299.