Tumor phylogeography reveals block-shaped spatial heterogeneity and the mode of evolution in Hepatocellular Carcinoma
© 2024. The Author(s)..
Solid tumors are complex ecosystems with heterogeneous 3D structures, but the spatial intra-tumor heterogeneity (sITH) at the macroscopic (i.e., whole tumor) level is under-explored. Using a phylogeographic approach, we sequence genomes and transcriptomes from 235 spatially informed sectors across 13 hepatocellular carcinomas (HCC), generating one of the largest datasets for studying sITH. We find that tumor heterogeneity in HCC segregates into spatially variegated blocks with large genotypic and phenotypic differences. By dissecting the transcriptomic heterogeneity, we discover that 30% of patients had a "spatially competing distribution" (SCD), where different spatial blocks have distinct transcriptomic subtypes co-existing within a tumor, capturing the critical transition period in disease progression. Interestingly, the tumor regions with more advanced transcriptomic subtypes (e.g., higher cell cycle) often take clonal dominance with a wider geographic range, rejecting neutral evolution for SCD patients. Extending the statistical tests for detecting natural selection to many non-SCD patients reveal varying levels of selective signal across different tumors, implying that many evolutionary forces including natural selection and geographic isolation can influence the overall pattern of sITH. Taken together, tumor phylogeography unravels a dynamic landscape of sITH, pinpointing important evolutionary and clinical consequences of spatial heterogeneity in cancer.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
|---|---|
| Enthalten in: |
Nature communications - 15(2024), 1 vom: 12. Apr., Seite 3169 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Liu, Xiaodong [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
|---|
| Anmerkungen: |
Date Completed 15.04.2024 Date Revised 25.04.2024 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1038/s41467-024-47541-9 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM370986687 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM370986687 | ||
| 003 | DE-627 | ||
| 005 | 20240425234118.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240413s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41467-024-47541-9 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1386.xml |
| 035 | |a (DE-627)NLM370986687 | ||
| 035 | |a (NLM)38609353 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Liu, Xiaodong |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Tumor phylogeography reveals block-shaped spatial heterogeneity and the mode of evolution in Hepatocellular Carcinoma |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 15.04.2024 | ||
| 500 | |a Date Revised 25.04.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024. The Author(s). | ||
| 520 | |a Solid tumors are complex ecosystems with heterogeneous 3D structures, but the spatial intra-tumor heterogeneity (sITH) at the macroscopic (i.e., whole tumor) level is under-explored. Using a phylogeographic approach, we sequence genomes and transcriptomes from 235 spatially informed sectors across 13 hepatocellular carcinomas (HCC), generating one of the largest datasets for studying sITH. We find that tumor heterogeneity in HCC segregates into spatially variegated blocks with large genotypic and phenotypic differences. By dissecting the transcriptomic heterogeneity, we discover that 30% of patients had a "spatially competing distribution" (SCD), where different spatial blocks have distinct transcriptomic subtypes co-existing within a tumor, capturing the critical transition period in disease progression. Interestingly, the tumor regions with more advanced transcriptomic subtypes (e.g., higher cell cycle) often take clonal dominance with a wider geographic range, rejecting neutral evolution for SCD patients. Extending the statistical tests for detecting natural selection to many non-SCD patients reveal varying levels of selective signal across different tumors, implying that many evolutionary forces including natural selection and geographic isolation can influence the overall pattern of sITH. Taken together, tumor phylogeography unravels a dynamic landscape of sITH, pinpointing important evolutionary and clinical consequences of spatial heterogeneity in cancer | ||
| 650 | 4 | |a Journal Article | |
| 700 | 1 | |a Zhang, Ke |e verfasserin |4 aut | |
| 700 | 1 | |a Kaya, Neslihan A |e verfasserin |4 aut | |
| 700 | 1 | |a Jia, Zhe |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Dafei |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Tingting |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Zhiyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Sinan |e verfasserin |4 aut | |
| 700 | 1 | |a Hillmer, Axel M |e verfasserin |4 aut | |
| 700 | 1 | |a Wuestefeld, Torsten |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Jin |e verfasserin |4 aut | |
| 700 | 1 | |a Chan, Yun Shen |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Zheng |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Liang |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Li |e verfasserin |4 aut | |
| 700 | 1 | |a Zhai, Weiwei |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Nature communications |d 2010 |g 15(2024), 1 vom: 12. Apr., Seite 3169 |w (DE-627)NLM199274525 |x 2041-1723 |7 nnns |
| 773 | 1 | 8 | |g volume:15 |g year:2024 |g number:1 |g day:12 |g month:04 |g pages:3169 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1038/s41467-024-47541-9 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 15 |j 2024 |e 1 |b 12 |c 04 |h 3169 | ||