Fatemeh Ardeshir-Larijani1, Priyanka Bhateja1, Mary Beth Lipka1, Neelesh Sharma2, Pingfu Fu3, Afshin Dowlati4. 1. Division of Hematology and Oncology, Case Western Reserve University, Cleveland, OH. 2. Division of Hematology and Oncology, Case Western Reserve University, University Hospitals Seidman Cancer Center, Cleveland, OH. 3. Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH. 4. Division of Hematology and Oncology, Case Western Reserve University, University Hospitals Seidman Cancer Center, Cleveland, OH. Electronic address: afshin.dowlati@case.edu.
Abstract
BACKGROUND: Mixed-lineage leukemia protein 2 (MLL2 or KMT2D) is a histone methyltransferase whose mutation has been associated with a poor prognosis in cancer. We compared the characteristics and significance of KMT2D alterations in non-small-cell lung cancer (NSCLC) with those in small cell lung cancer (SCLC). PATIENTS AND METHODS: Tumors from 194 NSCLC patients with locally advanced or advanced disease and 64 SCLC patients underwent targeted-exome sequencing. The association of KMT2D mutation with overall survival (OS) and progression-free survival (PFS) was measured using Kaplan-Meier methods and further evaluated using multivariable Cox proportional hazards regression model adjusting for known clinical prognostic features. RESULTS: The KMT2D mutation rate was 17.5% (34 of 194) in NSCLC. Patients with mutant KMT2D had significantly lower median OS (9.97 vs. 30.2 months; P < .0001) and median PFS (8.46 vs. 24.1 months; P = .0004) compared with patients with wild-type KMT2D. The KMT2D mutation was significantly more common in females (P = .017). Using a multivariate Cox regression model, KMT2D mutation was one of the most significant prognostic factors in NSCLC: hazard ratio (HR) for OS, 2.79 (95% confidence interval [CI], 1.8-4.33; P < .0001) and HR for PFS, 1.99 (95% CI, 1.32-3.01; P = .001). In contrast, the KMT2D mutation rate in SCLC was 32.8% (21 of 64) and showed no sex bias (P = .874). No significant change was found in survival in association with the KMT2D mutation in SCLC (OS, P = .952; PFS, P = .744). CONCLUSION: The KMT2D mutation was associated with reduced survival in NSCLC but not in SCLC.
BACKGROUND: Mixed-lineage leukemia protein 2 (MLL2 or KMT2D) is a histone methyltransferase whose mutation has been associated with a poor prognosis in cancer. We compared the characteristics and significance of KMT2D alterations in non-small-cell lung cancer (NSCLC) with those in small cell lung cancer (SCLC). PATIENTS AND METHODS: Tumors from 194 NSCLCpatients with locally advanced or advanced disease and 64 SCLCpatients underwent targeted-exome sequencing. The association of KMT2D mutation with overall survival (OS) and progression-free survival (PFS) was measured using Kaplan-Meier methods and further evaluated using multivariable Cox proportional hazards regression model adjusting for known clinical prognostic features. RESULTS: The KMT2D mutation rate was 17.5% (34 of 194) in NSCLC. Patients with mutant KMT2D had significantly lower median OS (9.97 vs. 30.2 months; P < .0001) and median PFS (8.46 vs. 24.1 months; P = .0004) compared with patients with wild-type KMT2D. The KMT2D mutation was significantly more common in females (P = .017). Using a multivariate Cox regression model, KMT2D mutation was one of the most significant prognostic factors in NSCLC: hazard ratio (HR) for OS, 2.79 (95% confidence interval [CI], 1.8-4.33; P < .0001) and HR for PFS, 1.99 (95% CI, 1.32-3.01; P = .001). In contrast, the KMT2D mutation rate in SCLC was 32.8% (21 of 64) and showed no sex bias (P = .874). No significant change was found in survival in association with the KMT2D mutation in SCLC (OS, P = .952; PFS, P = .744). CONCLUSION: The KMT2D mutation was associated with reduced survival in NSCLC but not in SCLC.
Authors: Sietse M Aukema; Selina Glaser; Mari F C M van den Hout; Sonja Dahlum; Marinus J Blok; Morten Hillmer; Julia Kolarova; Raf Sciot; Dina A Schott; Reiner Siebert; Constance T R M Stumpel Journal: Fam Cancer Date: 2022-07-19 Impact factor: 2.446
Authors: Leo Y Luo; Robert M Samstein; Rosalind Dick-Godfrey; Baho Sidiqi; Chunyu Wang; Federica Oro; Mark Sonnick; Paul K Paik; Jamie E Chaft; Narek Shaverdian; Daniel R Gomez; Andreas Rimner; Abraham J Wu Journal: Adv Radiat Oncol Date: 2020-11-14
Authors: Hua You; Zijun Y Xu-Monette; Li Wei; Harry Nunns; Máté L Nagy; Govind Bhagat; Xiaosheng Fang; Feng Zhu; Carlo Visco; Alexandar Tzankov; Karen Dybkaer; April Chiu; Wayne Tam; Youli Zu; Eric D Hsi; Fredrick B Hagemeister; Jooryung Huh; Maurilio Ponzoni; Andrés J M Ferreri; Michael B Møller; Benjamin M Parsons; J Han Van Krieken; Miguel A Piris; Jane N Winter; Yong Li; Qingyan Au; Bing Xu; Maher Albitar; Ken H Young Journal: Oncoimmunology Date: 2021-07-20 Impact factor: 8.110