Very large hidden genetic diversity in one single tumor: evidence for tumors-in-tumor.
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Embargo End Date
ICR Authors
Authors
Chen, B
Wu, X
Ruan, Y
Zhang, Y
Cai, Q
Zapata, L
Wu, C-I
Lan, P
Wen, H
Wu, X
Ruan, Y
Zhang, Y
Cai, Q
Zapata, L
Wu, C-I
Lan, P
Wen, H
Document Type
Journal Article
Date
2022-12-12
Date Accepted
2022-10-20
Abstract
Despite the concern of within-tumor genetic diversity, this diversity is in fact limited by the kinship among cells in the tumor. Indeed, genomic studies have amply supported the 'Nowell dogma' whereby cells of the same tumor descend from a single progenitor cell. In parallel, genomic data also suggest that the diversity could be >10-fold larger if tumor cells are of multiple origins. We develop an evolutionary hypothesis that a single tumor may often harbor multiple cell clones of independent origins, but only one would be large enough to be detected. To test the hypothesis, we search for independent tumors within a larger one (or tumors-in-tumor). Very high density sampling was done on two cases of colon tumors. Case 1 indeed has 13 independent clones of disparate sizes, many having heavy mutation burdens and potentially highly tumorigenic. In Case 2, despite a very intensive search, only two small independent clones could be found. The two cases show very similar movements and metastasis of the dominant clone. Cells initially move actively in the expanding tumor but become nearly immobile in late stages. In conclusion, tumors-in-tumor are plausible but could be very demanding to find. Despite their small sizes, they can enhance the within-tumor diversity by orders of magnitude. Such increases may contribute to the missing genetic diversity associated with the resistance to cancer therapy.
Citation
National Science Review, 2022, 9 (12), pp. nwac250 -
Source Title
National Science Review
Publisher
OXFORD UNIV PRESS
ISSN
2095-5138
eISSN
2053-714X
2053-714X
2053-714X
Collections
Research Team
Directorate for CEC