Genomic differences of patients with hematologic malignancies in different age groups
Abstract Hematologic malignancies cause significant morbidity/mortality in both children and young adults (CYAs) as well as older adults (OAs). Yet their biological underpinnings remain inadequately understood. Here, we analyzed clinical and genomic disparities between CYAs and OAs in various hemato...
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Nature Portfolio
2024-12-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-024-07293-0 |
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| author | Xiaodi Yang Qian Wang Yuhua Sun Ziding Zhang Stefan Wuchty Zeyin Liang Yujun Dong |
| author_facet | Xiaodi Yang Qian Wang Yuhua Sun Ziding Zhang Stefan Wuchty Zeyin Liang Yujun Dong |
| author_sort | Xiaodi Yang |
| collection | DOAJ |
| description | Abstract Hematologic malignancies cause significant morbidity/mortality in both children and young adults (CYAs) as well as older adults (OAs). Yet their biological underpinnings remain inadequately understood. Here, we analyzed clinical and genomic disparities between CYAs and OAs in various hematologic malignancies. We found substantial differences in clinical features such as patient sex, ethnicity, metastasis rates, and tumor subtypes. Genomically, most CYA hematologic malignancies indicated lower mutational burden. Subsequently, we identified differentially mutated genes (DMGs) with varying mutation rates between CYAs and OAs, noting fewer mutations in CYAs for most genes such as TP53, TET2, and DNMT3A. In contrast, several DMGs (i.e., NRAS, KRAS, SMARCA4, ID3, PTPN11, WT1, and KIT) were overrepresented in CYAs. We further investigated human protein interacting partners of these identified DMGs that were highly mutated in CYAs/OAs, respectively, and found significant differences in network topological and functional roles. Notably, CYA malignancies demonstrated extensive copy number alterations (CNAs) and more driver gene fusions. In particular, four CNA differential genes (i.e., ARID1B, MYB, TP53, and ESR1) were overrepresented as amplifications and deletions in CYAs and OAs, respectively. Ultimately, we demonstrated a landscape comparative view of clinically actionable genetic events in CYAs and OAs, providing clues for age-related personalized treatment. |
| format | Article |
| id | doaj-art-83e5bdbbbd8b45cfb386782792a348a9 |
| institution | OA Journals |
| issn | 2399-3642 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
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| series | Communications Biology |
| spelling | doaj-art-83e5bdbbbd8b45cfb386782792a348a92025-08-20T02:30:59ZengNature PortfolioCommunications Biology2399-36422024-12-017111210.1038/s42003-024-07293-0Genomic differences of patients with hematologic malignancies in different age groupsXiaodi Yang0Qian Wang1Yuhua Sun2Ziding Zhang3Stefan Wuchty4Zeyin Liang5Yujun Dong6Department of Hematology, Peking University First HospitalDepartment of Hematology, Peking University First HospitalDepartment of Hematology, Peking University First HospitalCollege of Biological Sciences, China Agricultural UniversityDepartment of Computer Science, University of MiamiDepartment of Hematology, Peking University First HospitalDepartment of Hematology, Peking University First HospitalAbstract Hematologic malignancies cause significant morbidity/mortality in both children and young adults (CYAs) as well as older adults (OAs). Yet their biological underpinnings remain inadequately understood. Here, we analyzed clinical and genomic disparities between CYAs and OAs in various hematologic malignancies. We found substantial differences in clinical features such as patient sex, ethnicity, metastasis rates, and tumor subtypes. Genomically, most CYA hematologic malignancies indicated lower mutational burden. Subsequently, we identified differentially mutated genes (DMGs) with varying mutation rates between CYAs and OAs, noting fewer mutations in CYAs for most genes such as TP53, TET2, and DNMT3A. In contrast, several DMGs (i.e., NRAS, KRAS, SMARCA4, ID3, PTPN11, WT1, and KIT) were overrepresented in CYAs. We further investigated human protein interacting partners of these identified DMGs that were highly mutated in CYAs/OAs, respectively, and found significant differences in network topological and functional roles. Notably, CYA malignancies demonstrated extensive copy number alterations (CNAs) and more driver gene fusions. In particular, four CNA differential genes (i.e., ARID1B, MYB, TP53, and ESR1) were overrepresented as amplifications and deletions in CYAs and OAs, respectively. Ultimately, we demonstrated a landscape comparative view of clinically actionable genetic events in CYAs and OAs, providing clues for age-related personalized treatment.https://doi.org/10.1038/s42003-024-07293-0 |
| spellingShingle | Xiaodi Yang Qian Wang Yuhua Sun Ziding Zhang Stefan Wuchty Zeyin Liang Yujun Dong Genomic differences of patients with hematologic malignancies in different age groups Communications Biology |
| title | Genomic differences of patients with hematologic malignancies in different age groups |
| title_full | Genomic differences of patients with hematologic malignancies in different age groups |
| title_fullStr | Genomic differences of patients with hematologic malignancies in different age groups |
| title_full_unstemmed | Genomic differences of patients with hematologic malignancies in different age groups |
| title_short | Genomic differences of patients with hematologic malignancies in different age groups |
| title_sort | genomic differences of patients with hematologic malignancies in different age groups |
| url | https://doi.org/10.1038/s42003-024-07293-0 |
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