Integrated driver mutations profile of chinese gastrointestinal-natural killer/T-cell lymphoma
BackgroundOne of the most common nasal external sites in extranodal Natural Killer/T-cell lymphoma (NKTCL) is in the gastrointestinal (GI) system. Despite this, reports on gastrointestinal-Natural Killer/T-cell lymphoma (GI-NKTCL) are very few. To obtain a better understanding of this manifestation...
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.976762/full |
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| author | Shanshan Li Shanshan Li Tingzhi Liu Tingzhi Liu Hailing Liu Hailing Liu Xiaohui Zhai Xiaohui Zhai Taiyuan Cao Taiyuan Cao Hongen Yu Hongen Yu Wanjia Hong Wanjia Hong Xiaoru Lin Xiaoru Lin Ming Li Ming Li Yan Huang Yan Huang Jian Xiao Jian Xiao |
| author_facet | Shanshan Li Shanshan Li Tingzhi Liu Tingzhi Liu Hailing Liu Hailing Liu Xiaohui Zhai Xiaohui Zhai Taiyuan Cao Taiyuan Cao Hongen Yu Hongen Yu Wanjia Hong Wanjia Hong Xiaoru Lin Xiaoru Lin Ming Li Ming Li Yan Huang Yan Huang Jian Xiao Jian Xiao |
| author_sort | Shanshan Li |
| collection | DOAJ |
| description | BackgroundOne of the most common nasal external sites in extranodal Natural Killer/T-cell lymphoma (NKTCL) is in the gastrointestinal (GI) system. Despite this, reports on gastrointestinal-Natural Killer/T-cell lymphoma (GI-NKTCL) are very few. To obtain a better understanding of this manifestation of NKTCL, we conducted a retrospective study on GI-NKTCL to analyze its clinical features, genomic changes and immune infiltration.MethodsWe retrospectively collected patients diagnosed with GI-NKTCL in the Sixth Affiliated Hospital of Sun Yat-sen University from 2010 to 2020. From this cohort we obtained mutation data via whole exome sequencing.ResultsGenomic analysis from 15 patients with GI-NKTCL showed that the most common driving mutations were ARID1B(14%, 2/15), ERBB3(14%, 2/15), POT1(14%, 2/15), and TP53(14%, 2/15). In addition, we found the most common gene mutation in patients with GI-NKTCL to be RETSAT(29%, 4/15) and SNRNP70(21%, 3/15), and the most common hallmark pathway mutations to be G2M checkpoint pathway (10/15, 66.7%), E2F targets (8/15, 53.3%), estrogen response late (7/15, 46.7%), estrogen response early (7/15, 46.7%), apoptosis (7/15, 46.7%) and TNFA signaling via NFKB (7/15, 46.7%). In the ICIs-Miao cohort, SNRNP7-wild-type (WT) melanoma patients had significantly prolonged overall survival (OS) time compared with SNRNP7 mutant type (MT) melanoma patients. In the TCGA-UCEC cohort, the patients with RETSAT-MT or SNRNP7-MT had significantly increased expression of immune checkpoint molecules and upregulation of inflammatory immune cells.ConclusionsIn this study, we explored GI-NKTCL by means of genomic analysis, and identified the most common mutant genes (RETSAT and SNRNP70), pathway mutations (G2M checkpoint and E2F targets) in GI-NKTCL patients. Also, we explored the association between the common mutant genes and immune infiltration. Our aim is that our exploration of these genomic changes will aid in the discovery of new biomarkers and therapeutic targets for those with GI-NKTCL, and finally provide a theoretical basis for improving the treatment and prognosis of patients with GI-NKTCL. |
| first_indexed | 2024-04-11T21:49:10Z |
| format | Article |
| id | doaj.art-10d4508089564deabcf9bc42f82cc124 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-11T21:49:10Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj.art-10d4508089564deabcf9bc42f82cc1242022-12-22T04:01:18ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-08-011210.3389/fonc.2022.976762976762Integrated driver mutations profile of chinese gastrointestinal-natural killer/T-cell lymphomaShanshan Li0Shanshan Li1Tingzhi Liu2Tingzhi Liu3Hailing Liu4Hailing Liu5Xiaohui Zhai6Xiaohui Zhai7Taiyuan Cao8Taiyuan Cao9Hongen Yu10Hongen Yu11Wanjia Hong12Wanjia Hong13Xiaoru Lin14Xiaoru Lin15Ming Li16Ming Li17Yan Huang18Yan Huang19Jian Xiao20Jian Xiao21Department of Medical Oncology, The Sixth Affiliated Hospital of Sun-Yat Sen University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Medical Hematology, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Pathology, The Sixth Affiliated Hospital of Sun-Yat Sen University, Guangzhou, ChinaDepartment of Medical Oncology, The Sixth Affiliated Hospital of Sun-Yat Sen University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Medical Oncology, The Sixth Affiliated Hospital of Sun-Yat Sen University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Medical Oncology, The Sixth Affiliated Hospital of Sun-Yat Sen University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Medical Oncology, The Sixth Affiliated Hospital of Sun-Yat Sen University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Medical Oncology, The Sixth Affiliated Hospital of Sun-Yat Sen University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Medical Oncology, The Sixth Affiliated Hospital of Sun-Yat Sen University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Pathology, The Sixth Affiliated Hospital of Sun-Yat Sen University, Guangzhou, ChinaDepartment of Medical Oncology, The Sixth Affiliated Hospital of Sun-Yat Sen University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaBackgroundOne of the most common nasal external sites in extranodal Natural Killer/T-cell lymphoma (NKTCL) is in the gastrointestinal (GI) system. Despite this, reports on gastrointestinal-Natural Killer/T-cell lymphoma (GI-NKTCL) are very few. To obtain a better understanding of this manifestation of NKTCL, we conducted a retrospective study on GI-NKTCL to analyze its clinical features, genomic changes and immune infiltration.MethodsWe retrospectively collected patients diagnosed with GI-NKTCL in the Sixth Affiliated Hospital of Sun Yat-sen University from 2010 to 2020. From this cohort we obtained mutation data via whole exome sequencing.ResultsGenomic analysis from 15 patients with GI-NKTCL showed that the most common driving mutations were ARID1B(14%, 2/15), ERBB3(14%, 2/15), POT1(14%, 2/15), and TP53(14%, 2/15). In addition, we found the most common gene mutation in patients with GI-NKTCL to be RETSAT(29%, 4/15) and SNRNP70(21%, 3/15), and the most common hallmark pathway mutations to be G2M checkpoint pathway (10/15, 66.7%), E2F targets (8/15, 53.3%), estrogen response late (7/15, 46.7%), estrogen response early (7/15, 46.7%), apoptosis (7/15, 46.7%) and TNFA signaling via NFKB (7/15, 46.7%). In the ICIs-Miao cohort, SNRNP7-wild-type (WT) melanoma patients had significantly prolonged overall survival (OS) time compared with SNRNP7 mutant type (MT) melanoma patients. In the TCGA-UCEC cohort, the patients with RETSAT-MT or SNRNP7-MT had significantly increased expression of immune checkpoint molecules and upregulation of inflammatory immune cells.ConclusionsIn this study, we explored GI-NKTCL by means of genomic analysis, and identified the most common mutant genes (RETSAT and SNRNP70), pathway mutations (G2M checkpoint and E2F targets) in GI-NKTCL patients. Also, we explored the association between the common mutant genes and immune infiltration. Our aim is that our exploration of these genomic changes will aid in the discovery of new biomarkers and therapeutic targets for those with GI-NKTCL, and finally provide a theoretical basis for improving the treatment and prognosis of patients with GI-NKTCL.https://www.frontiersin.org/articles/10.3389/fonc.2022.976762/fulldriver genemutationgastrointestinal-natural killer/T-cell lymphoma (GI-NKTCL)immune infiltrationgenomic analysis |
| spellingShingle | Shanshan Li Shanshan Li Tingzhi Liu Tingzhi Liu Hailing Liu Hailing Liu Xiaohui Zhai Xiaohui Zhai Taiyuan Cao Taiyuan Cao Hongen Yu Hongen Yu Wanjia Hong Wanjia Hong Xiaoru Lin Xiaoru Lin Ming Li Ming Li Yan Huang Yan Huang Jian Xiao Jian Xiao Integrated driver mutations profile of chinese gastrointestinal-natural killer/T-cell lymphoma Frontiers in Oncology driver gene mutation gastrointestinal-natural killer/T-cell lymphoma (GI-NKTCL) immune infiltration genomic analysis |
| title | Integrated driver mutations profile of chinese gastrointestinal-natural killer/T-cell lymphoma |
| title_full | Integrated driver mutations profile of chinese gastrointestinal-natural killer/T-cell lymphoma |
| title_fullStr | Integrated driver mutations profile of chinese gastrointestinal-natural killer/T-cell lymphoma |
| title_full_unstemmed | Integrated driver mutations profile of chinese gastrointestinal-natural killer/T-cell lymphoma |
| title_short | Integrated driver mutations profile of chinese gastrointestinal-natural killer/T-cell lymphoma |
| title_sort | integrated driver mutations profile of chinese gastrointestinal natural killer t cell lymphoma |
| topic | driver gene mutation gastrointestinal-natural killer/T-cell lymphoma (GI-NKTCL) immune infiltration genomic analysis |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.976762/full |
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