‘BIG BANG’ THEORY OF CARCINOGENESIS

Check this new theory about carcinogenesis recently published!

We should discuss it at our next lab meeting.

A Big Bang model of human colorectal tumor growth

Andrea Sottoriva, Heyoun Kang, Zhicheng Ma, Trevor A Graham, Matthew P Salomon,  Junsong Zhao, Paul Marjoram, Kimberly Siegmund, Michael F Press, Darryl Shibata & Christina Curtis

Nature Genetics, 2015

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 producing numerous  intermixed subclones that are not subject to stringent selection and where both public (clonal) and most detectable private  (subclonal) alterations arise early during growth. Genomic profiling of 349 individual glands from 15 colorectal tumors showed  an absence of selective sweeps, uniformly high intratumoral heterogeneity (ITH) and subclone mixing in distant regions, as  postulated by our model. We also verified the prediction that most detectable ITH originates from early private alterations and  not from later clonal expansions, thus exposing the profile of the primordial tumor. Moreover, some tumors appear ‘born to   be bad’, with subclone mixing indicative of early malignant potential. This new model provides a quantitative framework   to interpret tumor growth dynamics and the origins of ITH, with important clinical implications.

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