Abstract 2137: Association of copy number aberrations with oral cancer metastasis and progression of pre-malignant oral lesions
Authors: Bhattachayra Aditi , Snijders Antoine M. , Roy Ritu , Tokuyasu Taku , Jordan Richard C. K. , Olshen Adam , Pinkel Daniel , Schmidt Brian L. , Albertson Donna G. 
Published: February 2011

The 5-year survival rate for oral squamous cell carcinoma (SCC) patients at 40% has not improved over the past 40 years. Since genomes of 75-80% of oral SCCs are characterized by regions of gains and losses, we investigated whether copy number aberrations could be used to address two important problems in oral cancer management - identification of (a) tumors with metastatic potential and (b) dysplastic lesions at risk for progression to cancer.

Neck metastasis, the most significant clinical factor responsible for death from oral cancer reduces survival by 50%. To determine if copy number aberrations would distinguish tumors with metastatic potential, we carried out array comparative genomic hybridization (CGH) on 26 N0 and 38 N+ cases with at least 5-year follow up (diagnosed between 1997 and 2005). In order to reduce the multiple testing correction, regions of recurrent aberration were identified in an independent set of 89 oral SCCs (Snijders et al. 2005). A comparison of the frequency of aberrations affecting these regions in the N0 and N+ cases revealed no significant differences between the N0 and N+ cases after correction for multiple testing.

We used a similar approach to determine if there are significant copy number differences between oral dysplasia and oral SCC. Most oral SCCs are preceded by precancerous lesions, characterized by varying degrees of dysplasia (graded from mild to severe). Transformation to oral SCC is associated with 16% of mild and 55% of moderate/severe dysplasia. Copy number profiles for 44 dysplasia samples comprised of approximately equal numbers of cases graded mild, moderate or severe were obtained by array CGH. Although fewer copy number changes were observed in dysplasia compared to SCC, gains of 3q, 8q and/or chromosome 20 were present at approximately equal frequencies in dysplasia and SCC. In addition, the rare narrow amplicons, characteristic of oral SCC (Snijders et al. 2005), were present in dysplasia. To identify copy number alterations distinguishing dysplasia and SCC, regions of recurrent aberration were defined in an independent set of oral SCCs (the 64 cases from the metastasis study described above). The frequency of these copy number alterations was compared between the dysplasia and the 89 SCC cases (Snijders et al. 2005). Gain of 7p, including EGFR in SCC was found to be significant after correction for multiple testing. This observation is consistent with previous reports of increased expression of EGFR with progression of dysplasia to cancer (Garnis et al., 1998). Since 20-25% of oral SCC harbor almost no copy number changes, suggesting that dysplasia lacking copy number changes may have potential to progress to SCC with chromosomally stable genomes, we suggest that measurement of EGFR expression and/or other genes on 7p may provide a more effective biomarker for dysplasia progression than 7p copy number.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2137.