7183 - Pan-cancer whole genome analyses of metastatic solid tumors

Background

Metastatic cancer is one of the major causes of death and is associated with poor treatment efficiency. A better understanding of the characteristics of late stage cancer is required to help tailor personalised treatment, reduce overtreatment and improve outcomes.

Methods

Here we describe the largest pan-cancer study of metastatic solid tumor genomes, including 2,520 whole genome-sequenced tumor-normal pairs, analyzed at a median depth of 106x and 38x respectively, and surveying over 70 million somatic variants.

Results

Metastatic lesions were found to be very diverse, with mutation characteristics reflecting those of the primary tumor types, although with high rates of whole genome duplication events (56%). Metastatic lesions are relatively homogeneous with the vast majority (96%) of driver mutations being clonal and up to 80% of tumor suppressor genes bi-allelically inactivated through different mutational mechanisms. For 62% of all patients, genetic variants that may be associated with outcome of approved or experimental therapies were detected. These actionable events were distributed over the various mutation types (single and multiple nucleotide variants, insertions and deletions, copy number alterations and structural variants) underlining the importance of comprehensive genomic tumor profiling for cancer precision medicine for advanced cancer treatment.

Conclusions

Whole genome sequencing on fresh biopsies of metastatic cancer is feasible and identifies not only new insights in genome biology but also new opportunities for patients with both approved and experimental agents. We have created the largest data base of whole genome sequenced metastatic cancer patients which continues to facilitate new precision medicine studies.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Hartwig Medical Foundation, Barcode for Life, Dutch Cancer Society.

Disclosure

E. Cuppen: Honoraria (self), Advisory / Consultancy: InteRNA technologies BV; Honoraria (institution), Advisory / Consultancy: Illumina; Full / Part-time employment, Officer / Board of Directors: Hartwig Medical Foundation. M.P. Lolkema: Advisory / Consultancy: Incyte; Advisory / Consultancy: Amgen; Advisory / Consultancy: Janssen Cilag BV; Advisory / Consultancy: Bayer; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Sanofi Aventis Netherlands BV. P. Roepman: Honoraria (institution), Advisory / Consultancy: Illumina. V.C.G. Tjan-Heijnen: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: E. Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca. C. van Herpen: Advisory / Consultancy: Bayer; Advisory / Consultancy: BMS; Advisory / Consultancy: Ipsen ; Advisory / Consultancy: MSD; Advisory / Consultancy: Regeneron; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): BMS ; Research grant / Funding (self): MSD; Research grant / Funding (self): Merck; Research grant / Funding (self): Ipen; Research grant / Funding (self): Novartis ; Research grant / Funding (self): Sanofi . E.F. Smit: Honoraria (institution): AstraZeneca ; Honoraria (institution): BMC; Honoraria (institution): Bayer; Honoraria (institution): Eli Lilly ; Honoraria (institution): MSD; Honoraria (institution): Merck ; Honoraria (institution): Novartis; Honoraria (institution): Pfizer; Honoraria (institution): Takeda; Honoraria (institution): Regeneron; Honoraria (institution): Roche ; Honoraria (institution): Seattle Genetrics; Advisory / Consultancy: Eli Lilly ; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Merck; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Roche. All other authors have declared no conflicts of interest.