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CEWG Seminar Series

upcoming seminar series

General Attendee Webinar Zoom Link: TBA

February 9, 2023

Thursday, February 9, 2023
11:00 am – 12:30 pm EST


Frank H. Laukien, PhD
Bruker Corporation, Harvard University, Boston, MA

Title: Active Vertical and Horizontal Multiomics Cancer Evolution at Different Timescales

Jeffrey P. Townsend, PhD

Elihu Professor of Biostatistics, Professor of Ecology and Evolutionary Biology, Yale School of Public Health, New Haven, CT

Title: “Why Me?”: The Mutagenic Origins of Cancer for Individual Tumors and Tumor Types

Abstract: It is natural for patients to want to understand the causes behind their calamities. To date, risk factors are nearly the only answer that science or medicine has been able to give patients who ask “why me?” or to public health officials that ask “why us?”. Recent research has revealed signatures of these mutational processes in the genomes of tumors, which has been an extraordinary contribution to our scientific understanding of tumorigenesis. However, knowledge of the mutational processes acting on our DNA does not on its own convey the cellular causation of cancer: many mutations are “passenger” mutations that do not affect progression. One must know which mutations are causative, which are not, and to what degree. In recent years we quantified the effect sizes of somatic nucleotide changes on cancer, i.e., the degree to which each nucleotide change contributes to the survival and proliferation of cancer cells in humans. In current research, we have described how the quantifications of mutation and selection in the evolution of cancer can be brought together to ascribe the causation of cancer to specific mutational processes. We are now able to quantify the contribution of each mutational process to cancer in individual patients (a far finer scale of discovery than corresponding epidemiological findings) via the selected protein site variants that those processes engender. Our results provide molecular validation of well-known correlative findings from the epidemiological literature—such as providing an explanation for the increased odds of KRAS mutation in tumor tissue of ever smokers compared to never smokers, as well as the increased odds of EGFR mutation in never smokers compared to ever smokers. We demonstrate that melanomas and lung cancers are largely attributable to the preventable, exogenous mutational processes of ultraviolet light and tobacco exposure, whereas gliomas and prostate adenocarcinoma tumors are largely attributable to endogenous processes associated with aging. Other potentially preventable mutational processes, such as mutations associated with pathogen exposure and APOBEC activity, account for a large proportion of the cancer effect within head and neck, bladder, cervical, and breast cancers.Furthermore, our results quantify the balance of endogenous processes (such as cytosine deamination associated with aging) and exogenous processes (such as smoking, ultraviolet light, or exposure to haloalkanes) contributing to 23 major cancer types—a balance that both validates the dangers of exogenous mutations and conveys our prospects for public health efforts toward the prevention of their carcinogenic effects.

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