Pathogenic mutations and overall survival in 3,084 patients with cancer: the Hellenic Cooperative Oncology Group Precision Medicine Initiative

Fountzilas, Elena and Kotoula, Vassiliki and Koliou, Georgia-Angeliki and Giannoulatou, Eleni and Gogas, Helen and Papadimitriou, Christos and Tikas, Ioannis and Zhang, Jianhua and Papadopoulou, Kyriaki and Zagouri, Flora and Christodoulou, Christos and Koutras, Angelos and Makatsoris, Thomas and Chrisafi, Sofia and Linardou, Helena and Varthalitis, Ioannis and Papatsibas, George and Razis, Evangelia and Papakostas, Pavlos and Samantas, Epaminontas and Aravantinos, Gerasimos and Bafaloukos, Dimitrios and Kosmidis, Paris and Koumarianou, Anna and Psyrri, Amanda and Pentheroudakis, Georgios and Pectasides, Dimitrios and Futreal, Andrew and Fountzilas, George and Tsimberidou, Apostolia M. (2020) Pathogenic mutations and overall survival in 3,084 patients with cancer: the Hellenic Cooperative Oncology Group Precision Medicine Initiative. Oncotarget, 11 (1). pp.1-14. ISSN 1949-2553

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Background: We evaluated the association between pathogenic mutations and overall survival (OS) in patients with cancer referred to Hellenic Cooperative Oncology Group-affiliated Departments. Patients and methods: Patients referred from 12/1980 to 1/2017 had molecular testing (for research) of archival tumor tissue collected at the time of first diagnosis (non-metastatic, 81%; metastatic, 19%). Tumor-specific gene panels (16-101 genes) were used to identify pathogenic mutations in clinically relevant genes. NGS genotyping was performed at the Laboratory of Molecular Oncology, Aristotle University of Thessaloniki. Annotation of mutations was performed at MD Anderson Cancer Center. Results: We analyzed 3,084 patients (median age, 57 years; men, 22%) with sequencing data. Overall, 1,775 (58% of 3,084) patients had pathogenic mutations. The median follow-up was 7.52 years (95% CI, 7.39-7.61). In patients with non-metastatic tumors, after stratification by tumor type, increasing age, higher grade, and histology other than adenocarcinoma were associated with shorter OS. OS was also shorter in patients with pathogenic TP53 (HR=1.36; p<0.001), MLL3 (HR=1.64; p=0.005), and BRCA1 (HR=1.46; p=0.047) mutations compared to wild-type genes. In multivariate analyses, independent prognostic factors predicting shorter OS were pathogenic mutations in TP53 (HR=1.37, p=0.002) and MLL3 (HR=1.50, p=0.027); increasing age (HR=1.02, p<0.001); and increasing grade (HR=1.46, p<0.001). In patients with metastatic cancer, older age and higher grade were associated with shorter OS and maintained their independent prognostic significance (increasing age, HR=1.03, p<0.001 and higher grade, HR=1.73, p<0.001). Conclusions: Analysis of molecular data reveals prognostic biomarkers, regardless of tissue or organ of origin to improve patient management.

Item Type: Article
Subjects: R Medicine > R Medicine (General)
Depositing User: Repository Administrator
Date Deposited: 06 Feb 2020 23:34
Last Modified: 14 Oct 2021 04:20

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