Molecular profiling identifies distinct subtypes across TP53 mutant tumors
Tumor protein 53 mutation (TP53mut) is one of the most important driver events facilitating tumorigenesis, which could induce a series of chain reactions to promote tumor malignant transformation. However, the malignancy progression patterns under TP53 mutation remain less known. Clarifying the mole...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
American Society for Clinical investigation
2023-10-01
|
| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.156485 |
| _version_ | 1797634383817998336 |
|---|---|
| author | Xin Chen Tianqi Liu Jianqi Wu Chen Zhu Gefei Guan Cunyi Zou Qing Guo Xiaolin Ren Chen Li Peng Cheng Wen Cheng Anhua Wu |
| author_facet | Xin Chen Tianqi Liu Jianqi Wu Chen Zhu Gefei Guan Cunyi Zou Qing Guo Xiaolin Ren Chen Li Peng Cheng Wen Cheng Anhua Wu |
| author_sort | Xin Chen |
| collection | DOAJ |
| description | Tumor protein 53 mutation (TP53mut) is one of the most important driver events facilitating tumorigenesis, which could induce a series of chain reactions to promote tumor malignant transformation. However, the malignancy progression patterns under TP53 mutation remain less known. Clarifying the molecular landscapes of TP53mut tumors will help us understand the process of tumor development and aid precise treatment. Here, we distilled genetic and epigenetic features altered in TP53mut cancers for cluster-of-clusters analysis. Using integrated classification, we derived 5 different subtypes of TP53mut patients. These subtypes have distinct features in genomic alteration, clinical relevance, microenvironment dysregulation, and potential therapeutics. Among the 5 subtypes, COCA3 was identified as the subtype with worst prognosis, causing an immunosuppressive microenvironment and immunotherapeutic resistance. Further drug efficacy research highlighted olaparib as the most promising therapeutic agents for COCA3 tumors. Importantly, the therapeutic efficacy of olaparib in COCA3 and immunotherapy in non-COCA3 tumors was validated via in vivo experimentation. Our study explored the important molecular events and developed a subtype classification system with distinct targeted therapy strategies for different subtypes of TP53mut tumors. These multiomics classification systems provide a valuable resource that significantly expands the knowledge of TP53mut tumors and may eventually benefit in clinical practice. |
| first_indexed | 2024-03-11T12:06:54Z |
| format | Article |
| id | doaj.art-b26d251db59b421da45b7485f6431d93 |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-03-11T12:06:54Z |
| publishDate | 2023-10-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-b26d251db59b421da45b7485f6431d932023-11-07T16:24:56ZengAmerican Society for Clinical investigationJCI Insight2379-37082023-10-01723Molecular profiling identifies distinct subtypes across TP53 mutant tumorsXin ChenTianqi LiuJianqi WuChen ZhuGefei GuanCunyi ZouQing GuoXiaolin RenChen LiPeng ChengWen ChengAnhua WuTumor protein 53 mutation (TP53mut) is one of the most important driver events facilitating tumorigenesis, which could induce a series of chain reactions to promote tumor malignant transformation. However, the malignancy progression patterns under TP53 mutation remain less known. Clarifying the molecular landscapes of TP53mut tumors will help us understand the process of tumor development and aid precise treatment. Here, we distilled genetic and epigenetic features altered in TP53mut cancers for cluster-of-clusters analysis. Using integrated classification, we derived 5 different subtypes of TP53mut patients. These subtypes have distinct features in genomic alteration, clinical relevance, microenvironment dysregulation, and potential therapeutics. Among the 5 subtypes, COCA3 was identified as the subtype with worst prognosis, causing an immunosuppressive microenvironment and immunotherapeutic resistance. Further drug efficacy research highlighted olaparib as the most promising therapeutic agents for COCA3 tumors. Importantly, the therapeutic efficacy of olaparib in COCA3 and immunotherapy in non-COCA3 tumors was validated via in vivo experimentation. Our study explored the important molecular events and developed a subtype classification system with distinct targeted therapy strategies for different subtypes of TP53mut tumors. These multiomics classification systems provide a valuable resource that significantly expands the knowledge of TP53mut tumors and may eventually benefit in clinical practice.https://doi.org/10.1172/jci.insight.156485GeneticsImmunology |
| spellingShingle | Xin Chen Tianqi Liu Jianqi Wu Chen Zhu Gefei Guan Cunyi Zou Qing Guo Xiaolin Ren Chen Li Peng Cheng Wen Cheng Anhua Wu Molecular profiling identifies distinct subtypes across TP53 mutant tumors JCI Insight Genetics Immunology |
| title | Molecular profiling identifies distinct subtypes across TP53 mutant tumors |
| title_full | Molecular profiling identifies distinct subtypes across TP53 mutant tumors |
| title_fullStr | Molecular profiling identifies distinct subtypes across TP53 mutant tumors |
| title_full_unstemmed | Molecular profiling identifies distinct subtypes across TP53 mutant tumors |
| title_short | Molecular profiling identifies distinct subtypes across TP53 mutant tumors |
| title_sort | molecular profiling identifies distinct subtypes across tp53 mutant tumors |
| topic | Genetics Immunology |
| url | https://doi.org/10.1172/jci.insight.156485 |
| work_keys_str_mv | AT xinchen molecularprofilingidentifiesdistinctsubtypesacrosstp53mutanttumors AT tianqiliu molecularprofilingidentifiesdistinctsubtypesacrosstp53mutanttumors AT jianqiwu molecularprofilingidentifiesdistinctsubtypesacrosstp53mutanttumors AT chenzhu molecularprofilingidentifiesdistinctsubtypesacrosstp53mutanttumors AT gefeiguan molecularprofilingidentifiesdistinctsubtypesacrosstp53mutanttumors AT cunyizou molecularprofilingidentifiesdistinctsubtypesacrosstp53mutanttumors AT qingguo molecularprofilingidentifiesdistinctsubtypesacrosstp53mutanttumors AT xiaolinren molecularprofilingidentifiesdistinctsubtypesacrosstp53mutanttumors AT chenli molecularprofilingidentifiesdistinctsubtypesacrosstp53mutanttumors AT pengcheng molecularprofilingidentifiesdistinctsubtypesacrosstp53mutanttumors AT wencheng molecularprofilingidentifiesdistinctsubtypesacrosstp53mutanttumors AT anhuawu molecularprofilingidentifiesdistinctsubtypesacrosstp53mutanttumors |