
乳がん細胞の進化過程において、まれな有利な「運転手」変異と頻繁な有害な「乗客」変異の相互作用を記述するタグ・オブ・ウォー・モデルを、モラン・モデルと分岐過程の2つのフレームワークで検討した。両モデルで得られる変異頻度スペクトルの特徴が良く一致することを示し、3つの乳がん検体のデータに当てはめることで、「乗客」変異が腫瘍形成過程で有害な選択圧を及ぼしていることを支持する結果を得た。


coremsg

Mutations arising during cancer evolution are typically categorized as either ‘drivers’ or ‘passengers’, depending on whether they increase the cell fitness. Recently, McFarland et al. introduced the Tug-of-War model for the joint effect of rare advantageous drivers and frequent but deleterious passengers. We examine this model under two common but distinct frameworks, the Moran model and the branching process. We show that frequently used statistics are similar between a version of the Moran model and the branching process conditioned on the final cell count, under different selection scenarios. We infer the selection coefficients for three breast cancer samples, resulting in good fits of the shape of their Site Frequency Spectra. All fitted values for the selective disadvantage of passenger mutations are nonzero, supporting the view that they exert deleterious selection during tumorigenesis that driver mutations must compensate.

### Competing Interest Statement

The authors have declared no competing interest.

Comparison of Tug-of-War Models Assuming Moran versus Branching Process Population Dynamics

乳がん細胞における-運転手-と-乗客-の変異の相互作用を仮定したタグ-オブ-ウォー-モデルの比較


乳がん細胞における「運転手」と「乗客」の変異の相互作用を仮定したタグ・オブ・ウォー・モデルの比較
