Oral Presentation 27th Lorne Cancer Conference 2015

Australian Melanoma Genome Project (#1)

James S Wilmott 1 , Peter Johansson 2 , Matthew A Field 3 , Valerie Jakrot 1 , John V Pearson 2 , Nicola Waddell 2 , Catherine A Shang 4 , Andrew Gilbert 4 , Jonathan Cebon 5 , Mark Shackleton 6 , Sean M Grimmond 7 , Anna Fitzgerald 4 , John F Thompson 1 , Nick Hayward 2 , Richard A Scolyer 8 , Graham J Mann 1 9
  1. Melanoma Institute Australia, North Sydney, NSW, Australia
  2. Oncogenomics Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
  3. Immunogenomics Laboratory, Australian National University, Canberra, ACT, Australia
  4. Bioplatforms Australia, Macquarie University, North Ryde, NSW, Australia
  5. Olivia Newton-John Cancer Research Institute, Austin Health, Heidelberg, VIC, Australia
  6. Melanoma Research Laboratory, Peter MacCallum Cancer Centre and Sir Peter MacCallum Department of Oncology, University of Melbourne, VIC, Australia
  7. Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia
  8. Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
  9. Centre for Cancer Research, University of Sydney at Westmead Millennium Institute, Westmead, NSW, Australia

Australia has the highest incidence of cutaneous melanoma worldwide, where it is the fourth most common cancer and a leading cause of cancer death in young adults. Late stage metastatic melanoma was until very recently usually rapidly fatal. However, inhibitors of the MAP kinase pathway and of immune checkpoint mechanisms have dramatically extended patient survival, highlighting the importance of identification of therapeutic targets in cancer through molecular characterization. Melanomas typically have very large numbers of somatic mutations, including some now understood to affect key driver genes both within and outside of coding regions. To comprehensively extend the molecular characterization of melanoma, the Australian Melanoma Genome Project (AMGP) was launched in August 2012 with the support of Melanoma Institute Australia (MIA), the Australian Government via Bioplatforms Australia, NSW Health and the Cancer Council NSW. The AMGP aims to analyse whole genomes from 500 primary and metastatic melanomas. To date, the majority of samples has been sourced from the MIA Biospecimen Bank, and thus have comprehensive, prospectively collected clinical annotation. Whole genome sequencing (WGS) has been performed and analysed to date on 220 samples from 202 patients: including 79 primary melanomas, 15 cell lines, and 126 metastases from various sites; 250 cases will be sequenced by the end of 2014, and the remaining 250 by mid-2015. WGS is being performed on the Illumina HiSeq 2000 and Xten platforms at Australian and Korean sequencing centres. Tumours are being analysed at ≥60X coverage, germline DNA at 40X, and cell lines at 40X. Mapping, alignment, variant calling and structural variant determination are being carried out with ICGC-compatible pipelines. Complementary RNAseq and methylome data are being obtained on a subset of cases, facilitating an integrated ‘omics’ approach to analysis. Data will be released in the public domain.