Abstract

Multiple primary lung cancers (MPLCs) harbour various genetic profiles among the tumours, even from individuals with same non-intrinsic risk factors. Paired mutational analyses were performed to obtain a census of mutational events in MPLC and assess their relationship with non-intrinsic risk factors. Thirty-eight surgical specimens from 17 patients diagnosed as MPLC were used. Extracted DNAs were sequenced for somatic mutations in 409 cancer-associated genes from a comprehensive cancer panel. We statistically analysed the correlation between each driver mutation frequency and non-intrinsic risk factors using Fisher's exact test, and whether genetic mutations occurred concomitantly or randomly in MPLC using an exact test. Comprehensive genetic analyses suggested different mutation profiles in tumours within the same individuals, with some exceptions. EGFR, KRAS, TP53, or PARP1 mutations were concomitantly detected in some MPLC cases. EGFR mutations were significantly more frequent in never or light smokers and females. Concomitant EGFR or KRAS mutations in MPLCs were significantly more frequent than expected by chance (P = .0023 and .0049, respectively) suggesting a more prominent role of non-intrinsic risk factors in EGFR and KRAS mutations than other mutations, which occurred more randomly. Concomitant EGFR or KRAS mutations were particularly prominent in never or light smokers and males.

Details

Title
Mutational landscape of multiple primary lung cancers and its correlation with non-intrinsic risk factors
Author
Izumi Motohiro 1 ; Oyanagi Jun 2 ; Sawa Kenji 3 ; Fukui Mitsuru 4 ; Ogawa Koichi 3 ; Matsumoto Yoshiya 3 ; Tani Yoko 5 ; Suzumura Tomohiro 5 ; Watanabe, Tetsuya 3 ; Kaneda Hiroyasu 5 ; Mitsuoka Shigeki 5 ; Asai Kazuhisa 3 ; Ohsawa Masahiko 6 ; Yamamoto Nobuyuki 2 ; Koh Yasuhiro 2 ; Kawaguchi Tomoya 7 

 Osaka City University, Department of Respiratory Medicine, Graduate School of Medicine, Osaka, Japan (GRID:grid.261445.0) (ISNI:0000 0001 1009 6411); Wakayama Medical University, Internal Medicine III, Wakayama, Japan (GRID:grid.412857.d) (ISNI:0000 0004 1763 1087) 
 Wakayama Medical University, Internal Medicine III, Wakayama, Japan (GRID:grid.412857.d) (ISNI:0000 0004 1763 1087) 
 Osaka City University, Department of Respiratory Medicine, Graduate School of Medicine, Osaka, Japan (GRID:grid.261445.0) (ISNI:0000 0001 1009 6411) 
 Osaka City University, Laboratory of Statistics, Graduate School of Medicine, Osaka, Japan (GRID:grid.261445.0) (ISNI:0000 0001 1009 6411) 
 Osaka City University, Department of Clinical Oncology, Graduate School of Medicine, Osaka, Japan (GRID:grid.261445.0) (ISNI:0000 0001 1009 6411) 
 Osaka City University, Department of Pathology, Graduate School of Medicine, Osaka, Japan (GRID:grid.261445.0) (ISNI:0000 0001 1009 6411) 
 Osaka City University, Department of Respiratory Medicine, Graduate School of Medicine, Osaka, Japan (GRID:grid.261445.0) (ISNI:0000 0001 1009 6411); Osaka City University, Department of Clinical Oncology, Graduate School of Medicine, Osaka, Japan (GRID:grid.261445.0) (ISNI:0000 0001 1009 6411) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2500162711
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.