Characterization of tumor evolution by functional clonality and phylogenetics in hepatocellular carcinoma
Abstract Hepatocellular carcinoma (HCC) is a molecularly heterogeneous solid malignancy, and its fitness may be shaped by how its tumor cells evolve. However, ability to monitor tumor cell evolution is hampered by the presence of numerous passenger mutations that do not provide any biological conseq...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-03-01
|
| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-024-06040-9 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832571378526584832 |
|---|---|
| author | Zeynep Kacar Eric Slud Doron Levy Julián Candia Anuradha Budhu Marshonna Forgues Xiaolin Wu Arati Raziuddin Bao Tran Jyoti Shetty Yotsawat Pomyen Jittiporn Chaisaingmongkol Siritida Rabibhadana Benjarath Pupacdi Vajarabhongsa Bhudhisawasdi Nirush Lertprasertsuke Chirayu Auewarakul Suleeporn Sangrajrang Chulabhorn Mahidol Mathuros Ruchirawat Xin Wei Wang |
| author_facet | Zeynep Kacar Eric Slud Doron Levy Julián Candia Anuradha Budhu Marshonna Forgues Xiaolin Wu Arati Raziuddin Bao Tran Jyoti Shetty Yotsawat Pomyen Jittiporn Chaisaingmongkol Siritida Rabibhadana Benjarath Pupacdi Vajarabhongsa Bhudhisawasdi Nirush Lertprasertsuke Chirayu Auewarakul Suleeporn Sangrajrang Chulabhorn Mahidol Mathuros Ruchirawat Xin Wei Wang |
| author_sort | Zeynep Kacar |
| collection | DOAJ |
| description | Abstract Hepatocellular carcinoma (HCC) is a molecularly heterogeneous solid malignancy, and its fitness may be shaped by how its tumor cells evolve. However, ability to monitor tumor cell evolution is hampered by the presence of numerous passenger mutations that do not provide any biological consequences. Here we develop a strategy to determine the tumor clonality of three independent HCC cohorts of 524 patients with diverse etiologies and race/ethnicity by utilizing somatic mutations in cancer driver genes. We identify two main types of tumor evolution, i.e., linear, and non-linear models where non-linear type could be further divided into classes, which we call shallow branching and deep branching. We find that linear evolving HCC is less aggressive than other types. GTF2IRD2B mutations are enriched in HCC with linear evolution, while TP53 mutations are the most frequent genetic alterations in HCC with non-linear models. Furthermore, we observe significant B cell enrichment in linear trees compared to non-linear trees suggesting the need for further research to uncover potential variations in immune cell types within genomically determined phylogeny types. These results hint at the possibility that tumor cells and their microenvironment may collectively influence the tumor evolution process. |
| format | Article |
| id | doaj-art-691639e7002e4697ac95cd9c7f146ab1 |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-691639e7002e4697ac95cd9c7f146ab12025-02-02T12:37:32ZengNature PortfolioCommunications Biology2399-36422024-03-017111110.1038/s42003-024-06040-9Characterization of tumor evolution by functional clonality and phylogenetics in hepatocellular carcinomaZeynep Kacar0Eric Slud1Doron Levy2Julián Candia3Anuradha Budhu4Marshonna Forgues5Xiaolin Wu6Arati Raziuddin7Bao Tran8Jyoti Shetty9Yotsawat Pomyen10Jittiporn Chaisaingmongkol11Siritida Rabibhadana12Benjarath Pupacdi13Vajarabhongsa Bhudhisawasdi14Nirush Lertprasertsuke15Chirayu Auewarakul16Suleeporn Sangrajrang17Chulabhorn Mahidol18Mathuros Ruchirawat19Xin Wei Wang20Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer InstituteDepartment of Mathematics, University of MarylandDepartment of Mathematics, University of MarylandLongitudinal Studies Section, Translational Gerontology Branch, National Institute on AgingLaboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer InstituteLaboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer InstituteCancer Research Technology ProgramCancer Research Technology ProgramCancer Research Technology ProgramCancer Research Technology ProgramLaboratory of Chemical Carcinogenesis, Chulabhorn Research InstituteLaboratory of Chemical Carcinogenesis, Chulabhorn Research InstituteLaboratory of Chemical Carcinogenesis, Chulabhorn Research InstituteLaboratory of Chemical Carcinogenesis, Chulabhorn Research InstituteFaculty of Medicine, Khon Kaen UniversityFaculty of Medicine, Chiang Mai UniversityPrincess Srisavangavadhana College of Medicine, Chulabhorn Royal AcademyNational Cancer InstituteLaboratory of Chemical Carcinogenesis, Chulabhorn Research InstituteLaboratory of Chemical Carcinogenesis, Chulabhorn Research InstituteLaboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer InstituteAbstract Hepatocellular carcinoma (HCC) is a molecularly heterogeneous solid malignancy, and its fitness may be shaped by how its tumor cells evolve. However, ability to monitor tumor cell evolution is hampered by the presence of numerous passenger mutations that do not provide any biological consequences. Here we develop a strategy to determine the tumor clonality of three independent HCC cohorts of 524 patients with diverse etiologies and race/ethnicity by utilizing somatic mutations in cancer driver genes. We identify two main types of tumor evolution, i.e., linear, and non-linear models where non-linear type could be further divided into classes, which we call shallow branching and deep branching. We find that linear evolving HCC is less aggressive than other types. GTF2IRD2B mutations are enriched in HCC with linear evolution, while TP53 mutations are the most frequent genetic alterations in HCC with non-linear models. Furthermore, we observe significant B cell enrichment in linear trees compared to non-linear trees suggesting the need for further research to uncover potential variations in immune cell types within genomically determined phylogeny types. These results hint at the possibility that tumor cells and their microenvironment may collectively influence the tumor evolution process.https://doi.org/10.1038/s42003-024-06040-9 |
| spellingShingle | Zeynep Kacar Eric Slud Doron Levy Julián Candia Anuradha Budhu Marshonna Forgues Xiaolin Wu Arati Raziuddin Bao Tran Jyoti Shetty Yotsawat Pomyen Jittiporn Chaisaingmongkol Siritida Rabibhadana Benjarath Pupacdi Vajarabhongsa Bhudhisawasdi Nirush Lertprasertsuke Chirayu Auewarakul Suleeporn Sangrajrang Chulabhorn Mahidol Mathuros Ruchirawat Xin Wei Wang Characterization of tumor evolution by functional clonality and phylogenetics in hepatocellular carcinoma Communications Biology |
| title | Characterization of tumor evolution by functional clonality and phylogenetics in hepatocellular carcinoma |
| title_full | Characterization of tumor evolution by functional clonality and phylogenetics in hepatocellular carcinoma |
| title_fullStr | Characterization of tumor evolution by functional clonality and phylogenetics in hepatocellular carcinoma |
| title_full_unstemmed | Characterization of tumor evolution by functional clonality and phylogenetics in hepatocellular carcinoma |
| title_short | Characterization of tumor evolution by functional clonality and phylogenetics in hepatocellular carcinoma |
| title_sort | characterization of tumor evolution by functional clonality and phylogenetics in hepatocellular carcinoma |
| url | https://doi.org/10.1038/s42003-024-06040-9 |
| work_keys_str_mv | AT zeynepkacar characterizationoftumorevolutionbyfunctionalclonalityandphylogeneticsinhepatocellularcarcinoma AT ericslud characterizationoftumorevolutionbyfunctionalclonalityandphylogeneticsinhepatocellularcarcinoma AT doronlevy characterizationoftumorevolutionbyfunctionalclonalityandphylogeneticsinhepatocellularcarcinoma AT juliancandia characterizationoftumorevolutionbyfunctionalclonalityandphylogeneticsinhepatocellularcarcinoma AT anuradhabudhu characterizationoftumorevolutionbyfunctionalclonalityandphylogeneticsinhepatocellularcarcinoma AT marshonnaforgues characterizationoftumorevolutionbyfunctionalclonalityandphylogeneticsinhepatocellularcarcinoma AT xiaolinwu characterizationoftumorevolutionbyfunctionalclonalityandphylogeneticsinhepatocellularcarcinoma AT aratiraziuddin characterizationoftumorevolutionbyfunctionalclonalityandphylogeneticsinhepatocellularcarcinoma AT baotran characterizationoftumorevolutionbyfunctionalclonalityandphylogeneticsinhepatocellularcarcinoma AT jyotishetty characterizationoftumorevolutionbyfunctionalclonalityandphylogeneticsinhepatocellularcarcinoma AT yotsawatpomyen characterizationoftumorevolutionbyfunctionalclonalityandphylogeneticsinhepatocellularcarcinoma AT jittipornchaisaingmongkol characterizationoftumorevolutionbyfunctionalclonalityandphylogeneticsinhepatocellularcarcinoma AT siritidarabibhadana characterizationoftumorevolutionbyfunctionalclonalityandphylogeneticsinhepatocellularcarcinoma AT benjarathpupacdi characterizationoftumorevolutionbyfunctionalclonalityandphylogeneticsinhepatocellularcarcinoma AT vajarabhongsabhudhisawasdi characterizationoftumorevolutionbyfunctionalclonalityandphylogeneticsinhepatocellularcarcinoma AT nirushlertprasertsuke characterizationoftumorevolutionbyfunctionalclonalityandphylogeneticsinhepatocellularcarcinoma AT chirayuauewarakul characterizationoftumorevolutionbyfunctionalclonalityandphylogeneticsinhepatocellularcarcinoma AT suleepornsangrajrang characterizationoftumorevolutionbyfunctionalclonalityandphylogeneticsinhepatocellularcarcinoma AT chulabhornmahidol characterizationoftumorevolutionbyfunctionalclonalityandphylogeneticsinhepatocellularcarcinoma AT mathurosruchirawat characterizationoftumorevolutionbyfunctionalclonalityandphylogeneticsinhepatocellularcarcinoma AT xinweiwang characterizationoftumorevolutionbyfunctionalclonalityandphylogeneticsinhepatocellularcarcinoma |