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Reconstructing single-cell karyotype alterations in colorectal cancer identifies punctuated and gradual diversification patterns.
(NATURE PORTFOLIO, 2021-08-01)
Central to tumor evolution is the generation of genetic diversity. However, the extent and patterns by which de novo karyotype alterations emerge and propagate within human tumors are not well understood, especially at ...
A Big Bang model of human colorectal tumor growth.
(NATURE PUBLISHING GROUP, 2015-03-01)
What happens in early, still undetectable human malignancies is unknown because direct observations are impractical. Here we present and validate a 'Big Bang' model, whereby tumors grow predominantly as a single expansion ...
Germline MBD4 deficiency causes a multi-tumor predisposition syndrome.
(CELL PRESS, 2022-05-05)
We report an autosomal recessive, multi-organ tumor predisposition syndrome, caused by bi-allelic loss-of-function germline variants in the base excision repair (BER) gene MBD4. We identified five individuals with bi-allelic ...
Between-region genetic divergence reflects the mode and tempo of tumor evolution.
(NATURE PUBLISHING GROUP, 2017-06-05)
Given the implications of tumor dynamics for precision medicine, there is a need to systematically characterize the mode of evolution across diverse solid tumor types. In particular, methods to infer the role of natural ...
First passage time analysis of spatial mutation patterns reveals sub-clonal evolutionary dynamics in colorectal cancer.
(PUBLIC LIBRARY SCIENCE, 2023-03-01)
The signature of early cancer dynamics on the spatial arrangement of tumour cells is poorly understood, and yet could encode information about how sub-clones grew within the expanding tumour. Novel methods of quantifying ...
Immunosuppressive niche engineering at the onset of human colorectal cancer.
(NATURE PORTFOLIO, 2022-04-04)
The evolutionary dynamics of tumor initiation remain undetermined, and the interplay between neoplastic cells and the immune system is hypothesized to be critical in transformation. Colorectal cancer (CRC) presents a unique ...
The evolutionary landscape of colorectal tumorigenesis.
(NATURE PORTFOLIO, 2018-10-01)
The evolutionary events that cause colorectal adenomas (benign) to progress to carcinomas (malignant) remain largely undetermined. Using multi-region genome and exome sequencing of 24 benign and malignant colorectal tumours, ...
Robust RNA-based in situ mutation detection delineates colorectal cancer subclonal evolution.
(NATURE PUBLISHING GROUP, 2017-12-08)
Intra-tumor heterogeneity (ITH) is a major underlying cause of therapy resistance and disease recurrence, and is a read-out of tumor growth. Current genetic ITH analysis methods do not preserve spatial context and may not ...