Comparative lesion sequencing provides insights into tumor evolution

By Siân Jones, Wei-Dong Chen, Giovanni Parmigiani, F. Diehl, Niko Beerenwinkel, T. Antal, Arne Traulsen, Martin A. Nowak, Christopher Siegel, Victor E. Velculescu and 4 more. Proceedings of the National Academy of Sciences of the United States of America, 2008

829 citations recorded by the source corpus.

We show that the times separating the birth of benign, invasive, and metastatic tumor cells can be determined by analysis of the mutations they have in common. When combined with prior clinical observations, these analyses suggest the following general conclusions about colorectal tumorigenesis: (i) It takes ≈17 years for a large benign tumor to evolve into an advanced cancer but <2 years for cells within that cancer to acquire the ability to metastasize; (ii) it requires few, if any, selective events to transform a highly invasive cancer cell into one with the capacity to metastasize; (iii) the process of cell culture ex vivo does not introduce new clonal mutations into colorectal tumor cell populations; and (iv) the rates at which point mutations develop in advanced cancers are similar to those of normal cells. These results have important implications for understanding human tumor pathogenesis, particularly those associated with metastasis.

Subfields: Cancer Research, Oncology, Pathology and Forensic Medicine

View Paper: https://www.semanticscholar.org/paper/a7f3a1beee7825d9778c867e208ab84682430936

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Citations in the corpus

Massive Genomic Rearrangement Acquired in a Single Catastrophic Event during Cancer Development (2011, background): “The prevailing dogma of cancer evolution is therefore one of ‘‘gradualism’’ in which acquisition of driver mutations occurs cumulatively over years to decades, resulting in incremental progression through increasingly malignant phenotypes (Jones et al., 2008).”
A Unique Metastasis Gene Signature Enables Prediction of Tumor Relapse in Early Stage Hepatocellular Carcinoma Patients (2010, neutral): “For example, genome analyses of primary colon tumors and paired metastases suggest that the genetic machinery that causes metastases may be hardwired into the tumor from the beginning (36).”
Parallel progression of primary tumours and metastases (2009, background): “Although most studies concur on mutational heterogeneity between paired samples, few report the superimposable or overlapping genotypical aberrations that are predicted by linear progressio”
Tumor Metastasis: Molecular Insights and Evolving Paradigms (2011, neutral): “An analogous conclusion was reached by sequencing 289 candidate exons in 10 patient-matched primary colorectal carcinomas and metastases (Jones et al., 2008).”
A molecularly annotated platform of patient-derived xenografts ("xenopatients") identifies HER2 as an effective therapeutic target in cetuximab-resistant colorectal cancer. (2011, background): “Although genetic coherence between fresh and mouse-expanded material has been demonstrated in the case of missense mutations (23), a”
Dependency of colorectal cancer on a TGF-beta-driven programme in stromal cells for metastasis initiation (2012, background): “In addition, global genome sequencing of metastatic lesions and primary CRCs revealed hardly any metastasis-specific mutation (Jones et al., 2008).”
Metastasis: from dissemination to organ-specific colonization (2009, background): “It is estimated that most genetic alterations for metastasis are acquired during progression to the invasive carcinoma stage, and few, if any, additional genetic events are required for the formation of distant liver metastase”
Cancer epigenetics: Tumor Heterogeneity, Plasticity of Stem-like States, and Drug Resistance (2014, background): “…in comparison to the spontaneous mutation rate in normal and cancer cells, which is about 10 10 mutations per nucleotide base pair per division (Jones et al., 2008), the error rate for gaining or losing methylation is far higher, estimated at 2 3 10 5 per CpG site per division (Yatabe et al.,…”