Clinical relevance of genetic heterogeneity among distinct liver metastatic deposits identified in CRC patients

Intra-patient inter-metastatic genetic heterogeneity is a pronounced feature of metastatic colorectal cancer, and the strong prognostic association reinforces its clinical relevance and places it as a key feature to be explored in future patient cohorts.

Scientist Anita Sveen - Photo: Terje Heiestad

In this collaborative study with Dept Oncology, Haukeland University Hospital and Dept Computer Science, University of Oslo, scientist Anita Sveen (photo) and colleagues in the Lothe group show that patients with a low level of heterogeneity, based on DNA copy number analyses of multiple metastases per patient, have a 4.6X and 3.6X longer three-year progression free and overall survival rate than patients with a high heterogeneity level.

The patient-wise heterogeneity score, based on pair-wise genetic distances among tumor deposits, was not associated with the number of metastatic lesions per patient or their genomic complexity, defined as the proportion of the genome with copy number aberrations. Previous chemotherapy exposure was associated with a higher patient-wise level of heterogeneity in subsequent metastases.

Link to article:
Intra-patient Inter-metastatic Genetic Heterogeneity in Colorectal Cancer as a Key Determinant of Survival after Curative Liver Resection.
Sveen A, Løes IM, Alagaratnam S, Nilsen G, Høland M, Lingjærde OC, Sorbye H, Berg KC, Horn A, Angelsen JH, Knappskog S, Lønning PE, Lothe RA.
PLoS Genet. 2016 Jul 29;12(7):e1006225. doi: 10.1371/journal.pgen.1006225. eCollection 2016 Jul.