Genomic heterogeneity in colorectal primary and liver metastases samples

Patch A-M1, Kawamata F2,3, Behrenbruch C4,5, Nones K6, Kazakoff S6, Addala V6, Pearson JV7, Hollande F4, Waddell N6 and Whitehall VLJ2

  1. Clinical Genomics, QIMR Berghofer Medical Research Institute, Queensland, Australia.
  2. Conjoint Gastroenterology Laboratory, QIMR Berghofer Medical Research Institute, Queensland, Australia.
  3. Hokkaido University Graduate School of Medicine, Sapporo, Japan.
  4. Department of Clinical Pathology, The University of Melbourne, Victoria, Australia.
  5. Department of Oncology, Sir Peter MacCallum Cancer Centre, Victoria, Australia.
  6. Medical Genomics, QIMR Berghofer Medical Research Institute, Queensland, Australia.
  7. Genome Informatics, QIMR Berghofer Medical Research Institute, Queensland, Australia.

Colorectal cancer (CRC) is the third most common malignancy diagnosed worldwide and in Australia, with an estimated >16,500 Australians affected in 2017. At diagnosis around 25% of CRC patients have metastatic (stage IV) disease and a further 25% of patients initially diagnosed at stage II/III will relapse with metastatic disease. Unfortunately, 75% of patients presenting with metastatic disease will have surgically unresectable disease and are incurable. The 5-year survival of this group of patients is approximately 5%, almost ten times lower than patients with resectable disease. Treatment is palliative and there are essentially only three available cytotoxic agents, 5-fluorouracil, oxaliplatin and irinotecan. Newer targeted agents and immunotherapy only show benefit in a subset of patients. Different sites of disease such as the primary tumour compared with the metastasis will have heterogeneity in treatment response making the choice of therapy more complex. A personalised medicine strategy that enables selection of the most effective therapy based on the tumour’s molecular characteristics could provide more effective treatment options for patient management especially for those with unresectable metastatic disease. Therefore, we are investigating the heterogeneity between matched primary CRC and liver metastasis samples in the context of targetable treatments.