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Comparative lesion sequencing provides insights into tumor evolution.

ABSTRACT: 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 approximately 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.

SUBMITTER: Jones S

PROVIDER: S-EPMC2393770 | biostudies-literature | 2008 Mar

REPOSITORIES: biostudies-literature

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Comparative lesion sequencing provides insights into tumor evolution.

Jones Siân S Chen Wei-Dong WD Parmigiani Giovanni G Diehl Frank F Beerenwinkel Niko N Antal Tibor T Traulsen Arne A Nowak Martin A MA Siegel Christopher C Velculescu Victor E VE Kinzler Kenneth W KW Vogelstein Bert B Willis Joseph J Markowitz Sanford D SD

Proceedings of the National Academy of Sciences of the United States of America 20080312 11

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 approximately 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 an ...[more]

PMID: 18337506

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Project description:DPANN is known as highly diverse, globally widespread, and mostly ectosymbiotic archaeal superphylum. However, this group of archaea was overlooked for a long time, and there were limited in-depth studies reported. In this investigation, 41 metagenome-assembled genomes (MAGs) belonging to the DPANN superphylum were recovered (18 MAGs had average nucleotide identity [ANI] values of <95% and a percentage of conserved proteins [POCP] of >50%, while 14 MAGs showed a POCP of <50%), which were analyzed comparatively with 515 other published DPANN genomes. Mismatches to known 16S rRNA gene primers were identified among 16S rRNA genes of DPANN archaea. Numbers of gene families lost (mostly related to energy and amino acid metabolism) were over three times greater than those gained in the evolution of DPANN archaea. Lateral gene transfer (LGT; ∼45.5% was cross-domain) had facilitated niche adaption of the DPANN archaea, ensuring a delicate equilibrium of streamlined genomes with efficient niche-adaptive strategies. For instance, LGT-derived cytochrome bd ubiquinol oxidase and arginine deiminase in the genomes of "Candidatus Micrarchaeota" could help them better adapt to aerobic acidic mine drainage habitats. In addition, most DPANN archaea acquired enzymes for biosynthesis of extracellular polymeric substances (EPS) and transketolase/transaldolase for the pentose phosphate pathway from Bacteria. IMPORTANCE The domain Archaea is a key research model for gaining insights into the origin and evolution of life, as well as the relevant biogeochemical processes. The discovery of nanosized DPANN archaea has overthrown many aspects of microbiology. However, the DPANN superphylum still contains a vast genetic novelty and diversity that need to be explored. Comprehensively comparative genomic analysis on the DPANN superphylum was performed in this study, with an attempt to illuminate its metabolic potential, ecological distribution and evolutionary history. Many interphylum differences within the DPANN superphylum were found. For example, Altiarchaeota had the biggest genome among DPANN phyla, possessing many pathways missing in other phyla, such as formaldehyde assimilation and the Wood-Ljungdahl pathway. In addition, LGT acted as an important force to provide DPANN archaeal genetic flexibility that permitted the occupation of diverse niches. This study has advanced our understanding of the diversity and genome evolution of archaea.

Dataset Information

Comparative lesion sequencing provides insights into tumor evolution.

Publications

Comparative lesion sequencing provides insights into tumor evolution.

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