Mutational landscape of multiple primary lung cancers and its correlation with non-intrinsic risk factors
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 ri...
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2021
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oai:doaj.org-article:9ef2d46178a24918ac220878f41f5e8c2021-12-02T13:34:32ZMutational landscape of multiple primary lung cancers and its correlation with non-intrinsic risk factors10.1038/s41598-021-83609-y2045-2322https://doaj.org/article/9ef2d46178a24918ac220878f41f5e8c2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83609-yhttps://doaj.org/toc/2045-2322Abstract 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.Motohiro IzumiJun OyanagiKenji SawaMitsuru FukuiKoichi OgawaYoshiya MatsumotoYoko TaniTomohiro SuzumuraTetsuya WatanabeHiroyasu KanedaShigeki MitsuokaKazuhisa AsaiMasahiko OhsawaNobuyuki YamamotoYasuhiro KohTomoya KawaguchiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021) |
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Medicine R Science Q |
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Medicine R Science Q Motohiro Izumi Jun Oyanagi Kenji Sawa Mitsuru Fukui Koichi Ogawa Yoshiya Matsumoto Yoko Tani Tomohiro Suzumura Tetsuya Watanabe Hiroyasu Kaneda Shigeki Mitsuoka Kazuhisa Asai Masahiko Ohsawa Nobuyuki Yamamoto Yasuhiro Koh Tomoya Kawaguchi Mutational landscape of multiple primary lung cancers and its correlation with non-intrinsic risk factors |
| description |
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. |
| format |
article |
| author |
Motohiro Izumi Jun Oyanagi Kenji Sawa Mitsuru Fukui Koichi Ogawa Yoshiya Matsumoto Yoko Tani Tomohiro Suzumura Tetsuya Watanabe Hiroyasu Kaneda Shigeki Mitsuoka Kazuhisa Asai Masahiko Ohsawa Nobuyuki Yamamoto Yasuhiro Koh Tomoya Kawaguchi |
| author_facet |
Motohiro Izumi Jun Oyanagi Kenji Sawa Mitsuru Fukui Koichi Ogawa Yoshiya Matsumoto Yoko Tani Tomohiro Suzumura Tetsuya Watanabe Hiroyasu Kaneda Shigeki Mitsuoka Kazuhisa Asai Masahiko Ohsawa Nobuyuki Yamamoto Yasuhiro Koh Tomoya Kawaguchi |
| author_sort |
Motohiro Izumi |
| title |
Mutational landscape of multiple primary lung cancers and its correlation with non-intrinsic risk factors |
| title_short |
Mutational landscape of multiple primary lung cancers and its correlation with non-intrinsic risk factors |
| title_full |
Mutational landscape of multiple primary lung cancers and its correlation with non-intrinsic risk factors |
| title_fullStr |
Mutational landscape of multiple primary lung cancers and its correlation with non-intrinsic risk factors |
| title_full_unstemmed |
Mutational landscape of multiple primary lung cancers and its correlation with non-intrinsic risk factors |
| title_sort |
mutational landscape of multiple primary lung cancers and its correlation with non-intrinsic risk factors |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/9ef2d46178a24918ac220878f41f5e8c |
| work_keys_str_mv |
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