The end of the genetic paradigm of cancer.
Genome sequencing of cancer and normal tissues, alongside single-cell transcriptomics, continues to produce findings that challenge the idea that cancer is a 'genetic disease', as posited by the somatic mutation theory (SMT). In this prevailing paradigm, tumorigenesis is caused by cancer-d...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2025-03-01
|
| Series: | PLoS Biology |
| Online Access: | https://doi.org/10.1371/journal.pbio.3003052 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850161024478478336 |
|---|---|
| author | Sui Huang Ana M Soto Carlos Sonnenschein |
| author_facet | Sui Huang Ana M Soto Carlos Sonnenschein |
| author_sort | Sui Huang |
| collection | DOAJ |
| description | Genome sequencing of cancer and normal tissues, alongside single-cell transcriptomics, continues to produce findings that challenge the idea that cancer is a 'genetic disease', as posited by the somatic mutation theory (SMT). In this prevailing paradigm, tumorigenesis is caused by cancer-driving somatic mutations and clonal expansion. However, results from tumor sequencing, motivated by the genetic paradigm itself, create apparent 'paradoxes' that are not conducive to a pure SMT. But beyond genetic causation, the new results lend credence to old ideas from organismal biology. To resolve inconsistencies between the genetic paradigm of cancer and biological reality, we must complement deep sequencing with deep thinking: embrace formal theory and historicity of biological entities, and (re)consider non-genetic plasticity of cells and tissues. In this Essay, we discuss the concepts of cell state dynamics and tissue fields that emerge from the collective action of genes and of cells in their morphogenetic context, respectively, and how they help explain inconsistencies in the data in the context of SMT. |
| format | Article |
| id | doaj-art-2f36d295ee3c425189b8175b44f5d83c |
| institution | OA Journals |
| issn | 1544-9173 1545-7885 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj-art-2f36d295ee3c425189b8175b44f5d83c2025-08-20T02:22:59ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852025-03-01233e300305210.1371/journal.pbio.3003052The end of the genetic paradigm of cancer.Sui HuangAna M SotoCarlos SonnenscheinGenome sequencing of cancer and normal tissues, alongside single-cell transcriptomics, continues to produce findings that challenge the idea that cancer is a 'genetic disease', as posited by the somatic mutation theory (SMT). In this prevailing paradigm, tumorigenesis is caused by cancer-driving somatic mutations and clonal expansion. However, results from tumor sequencing, motivated by the genetic paradigm itself, create apparent 'paradoxes' that are not conducive to a pure SMT. But beyond genetic causation, the new results lend credence to old ideas from organismal biology. To resolve inconsistencies between the genetic paradigm of cancer and biological reality, we must complement deep sequencing with deep thinking: embrace formal theory and historicity of biological entities, and (re)consider non-genetic plasticity of cells and tissues. In this Essay, we discuss the concepts of cell state dynamics and tissue fields that emerge from the collective action of genes and of cells in their morphogenetic context, respectively, and how they help explain inconsistencies in the data in the context of SMT.https://doi.org/10.1371/journal.pbio.3003052 |
| spellingShingle | Sui Huang Ana M Soto Carlos Sonnenschein The end of the genetic paradigm of cancer. PLoS Biology |
| title | The end of the genetic paradigm of cancer. |
| title_full | The end of the genetic paradigm of cancer. |
| title_fullStr | The end of the genetic paradigm of cancer. |
| title_full_unstemmed | The end of the genetic paradigm of cancer. |
| title_short | The end of the genetic paradigm of cancer. |
| title_sort | end of the genetic paradigm of cancer |
| url | https://doi.org/10.1371/journal.pbio.3003052 |
| work_keys_str_mv | AT suihuang theendofthegeneticparadigmofcancer AT anamsoto theendofthegeneticparadigmofcancer AT carlossonnenschein theendofthegeneticparadigmofcancer AT suihuang endofthegeneticparadigmofcancer AT anamsoto endofthegeneticparadigmofcancer AT carlossonnenschein endofthegeneticparadigmofcancer |