Oral Presentation Joint Scientific Meeting of the Australian & NZ Head & Neck Cancer Society & NZ Association of Plastic Surgeons

A comparison of the genomic profiles of young and old Patients with oral squamous cell carcinoma demonstrates a higher rate of EGFR copy number variation in younger patients   (1435)

Laveniya Satgunaseelan 1 2 , Sean Porazinski 3 4 , Dario Strbenac 5 , Aji Istadi 3 , Cali Willet 6 , Tracy Chew 6 , Rosemarie Sadsad 6 , Carsten E Palme 7 , Jenny Lee 8 , Michael Boyer 8 , Jean YH Yang 5 9 , Jonathan R Clark 2 7 10 , Marina Pajic 3 4 , Ruta Gupta 1 2 7
  1. Department of Tissue Pathology and Diagnostic Oncology, NSW Health Pathology, Royal Prince Alfred Hospital, Sydney
  2. Sydney Medical School, Faculty of Medicine and Health Sciences, The University of Sydney, Sydney
  3. Personalised Cancer Therapeutics, Cancer Division, The Kinghorn Cancer Centre, Sydney
  4. St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney
  5. School of Mathematics and Statistics, The University of Sydney, Sydney
  6. The Sydney Informatics Hub, Core Research Facilities, The University of Sydney, Sydney
  7. Sydney Head and Neck Cancer Institute, Depart of Head and Neck Surgery, Chris O'Brien Lifehouse, Sydney
  8. Department of Medical Oncology, Chris O'Brien Lifehouse, Sydney
  9. Charles Perkins Centre, The University of Sydney, Sydney
  10. Royal Alfred Institute of Academic Surgery, Sydney

OSCC in patients under the age of 50 years is on the rise globally, with limited personalised treatment options. Our study uncovers a clinically actionable molecular profile in a well curated institutional cohort of OSCC patients <50 years (n=17), with validation utilising TCGA dataset (patients <50 years – n=9; patients >50 years – n=11). We demonstrate significant divergence at the genomic and transcriptomic level between these two age groups. Whole genome and transcriptomic sequencing revealed a subset of OSCC patients <50 years with EGFR amplification and increased EGFR RNA abundance. Functional assays using patient tumour-derived cell lines (PDCLs) demonstrated responsiveness to treatment with a panel of EGFR inhibitors in PDCLs with EGFR amplification. Encouragingly, afatinib, a second-generation EGFR tyrosine kinase inhibitor, proved an efficacious therapeutic opportunity. Our findings of EGFR amplification were validated with fluorescent in situ hybridisation (FISH). FISH is a widely available testing modality in diagnostic pathology laboratories, which can be readily used to identify suitable young patients for targeted therapy in the future.