TY - JOUR
T1 - Pathogenic mutations and overall survival in 3,084 patients with cancer
T2 - The Hellenic Cooperative oncology group precision medicine initiative
AU - Fountzilas, Elena
AU - Kotoula, Vassiliki
AU - Koliou, Georgia Angeliki
AU - Giannoulatou, Eleni
AU - Gogas, Helen
AU - Papadimitriou, Christos
AU - Tikas, Ioannis
AU - Zhang, Jianhua
AU - Papadopoulou, Kyriaki
AU - Zagouri, Flora
AU - Christodoulou, Christos
AU - Koutras, Angelos
AU - Makatsoris, Thomas
AU - Chrisafi, Sofia
AU - Linardou, Helena
AU - Varthalitis, Ioannis
AU - Papatsibas, George
AU - Razis, Evangelia
AU - Papakostas, Pavlos
AU - Samantas, Epaminontas
AU - Aravantinos, Gerasimos
AU - Bafaloukos, Dimitrios
AU - Kosmidis, Paris
AU - Koumarianou, Anna
AU - Psyrri, Amanda
AU - Pentheroudakis, Georgios
AU - Pectasides, Dimitrios
AU - Futreal, Andrew
AU - Fountzilas, George
AU - Tsimberidou, Apostolia M.
N1 - Publisher Copyright:
© 2020 Impact Journals LLC. All rights reserved.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - 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.
AB - 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.
KW - Actionable gene
KW - Next-generation sequencing
KW - Pathogenic mutation
KW - Precision oncology
KW - Prognosis
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U2 - 10.18632/oncotarget.27338
DO - 10.18632/oncotarget.27338
M3 - Article
C2 - 32002119
AN - SCOPUS:85078726926
SN - 1949-2553
VL - 11
SP - 1
EP - 14
JO - Oncotarget
JF - Oncotarget
IS - 1
ER -