High-depth sequencing of paired primary and metastatic tumours: Implications for personalised medicine. (October 2017)

• Record Type: Journal Article
• Authors: Grellety, T.; Lucchesi, C.; Hostein, I.; Auzanneau, C.; Khalifa, E.; Soubeyran, I.; Italiano, A.
• Is Part Of: European journal of cancer. Volume 84(2017)
• Page Start: 250
• Page End: 256
• Publication Date: 2017-10
• Subjects: Molecular screening -- Targeted therapies -- Next-generation sequencing -- Primary tumour -- Metastases; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2017.07.019
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: Background: Next-generation sequencing of large panel of genes had been associated with clinical benefit in a significant proportion of patients with advanced cancer. However, the molecular profile of the primary tumour from the initial surgical specimen might significantly differ from the molecular profile in a tumour sample obtained from a biopsy of a metastatic site. Patients and methods: We compare the genetic profile of primary tumours and paired metastases by using a large panel of cancer genes. Training and validation set including a total of 152 primary and metastatic tumour pairs were sequenced (up to 429 genes) focussing on variants described in the Catalogue of Somatic Mutations in Cancer (COSMIC). Results: Training and validation set including a total of 152 primary and metastatic tumour pairs were sequenced focussing on variants described in COSMIC. Agreement rate between the couples of primary and metastasis on COSMIC variants was 65% (24/37) and 43% (49/115) in the training and validation cohort, respectively. That rose to 74% (20/27) and 58% (42/73) when focussing on targetable mutations. In five cases, the discordance was related to appearance of secondary resistance mutation, giving a targetable refined agreement rate of 67% (67/100). Conclusion: Up to 40% of paired primary tumour/metastases have discordant molecular profile. Liquid biopsies may overcome, in the near future, the limits of tumour tissue genotyping. Highlights: We report the first large series comparing paired primary tumours and metastasis sequenced with a wide panel of genes. We found that up to 40% of paired primary tumour/metastases have discordant molecular profile. Genotyping the primary tumour may be inappropriate to guide systemic treatment in a significant proportion of cases. Discrepancies can be explained by heterogeneity and/or by therapeutic stress.