Biology subjects

Abegglen, L.

Publications and source records attributed to Abegglen, L..

3 recordsLinked to original sources

bioRxiv2023

Germline mutation rate predicts cancer mortality across 37 vertebrate species

The explanation for why some species are more susceptible to cancer than others remains an area of intense investigation. Cancer evolves in part through the accumulation of mutations and, therefore, we hypothesized that germline mutation rates would be associated with cancer prevalence and mortality across species. We collected previously published data on germline mutation rate and cancer mortality data for 37 vertebrate species. Germline mutation rate was positively correlated with cancer mortality (P = 0.008). Why animals with increased germline mutation rates die more from cancer remains an open question, however they may benefit from close monitoring for tumors due to hereditary cancer predisposition syndromes. Early diagnoses of cancer in these species may increase their chances of treatment and overall survival.

cancer biology↗

bioRxiv2023

Cancer Prevalence Across Vertebrates

Cancer is pervasive across multicellular species, but what explains differences in cancer prevalence across species? Using 16,049 necropsy records for 292 species spanning three clades (amphibians, sauropsids and mammals) we found that neoplasia and malignancy prevalence increases with adult weight (contrary to Petos Paradox) and somatic mutation rate, but decreases with gestation time. Evolution of cancer susceptibility appears to have undergone sudden shifts followed by stabilizing selection. Outliers for neoplasia prevalence include the common porpoise (<1.3%), the Rodrigues fruit bat (<1.6%) the black-footed penguin (<0.4%), ferrets (63%) and opossums (35%). Discovering why some species have particularly high or low levels of cancer may lead to a better understanding of cancer syndromes and novel strategies for the management and prevention of cancer. Statement of SignificanceEvolution has discovered mechanisms for suppressing cancer in a wide variety of species. By analyzing veterinary necropsy records we can identify species with exceptionally high or low cancer prevalence. Discovering the mechanisms of cancer susceptibility and resistance may help improve cancer prevention and explain cancer syndromes.

cancer biology↗

bioRxiv2018

Dynamics of the p53 response to ionizing and ultraviolet radiation

The tumor suppressor protein p53 compiles information about cellular stressors to make decisions on whether the cell should survive or undergo apoptosis. However, the p53 response depends on the source of damage, displaying a digital oscillatory response after ionizing radiation (IR) damage and a proportional non-oscillatory response following UV damage. We propose a mathematical model that qualitatively replicates this observed behavior. The difference in p53 dynamics in the model results from two mechanisms: IR damage is fully detected minutes after exposure while UV damage is detected over several hours; and the p53-controlled transcriptional response is dominated by inactive p53 following UV damage. In particular, we hypothesize that an unidentified positive feedback loop controlled by inactive p53 is required to maintain the qualitative high p53 response to UV damage. This work proposes an explanation for two distinct responses of p53 to DNA damage and how each response can lead to cell cycle arrest or apoptosis.\n\nAuthor summaryWe propose a mathematical model hypothesizing how the tumor suppressor protein p53 produces two contrasting dynamical responses in response to different types of DNA damage. In particular, we predict the existence of a positive feedback loop controlled by the inactive form of p53, which allows the cell to respond to slowly detected damage. The existence of differing dynamic responses by p53 has implications for our understanding of tumor development and possibly p53-related therapeutic strategies.

cancer biology↗