Chunling Hu, Anil Belur Nagaraj, Hermela Shimelis, Gemma Montalban, Kun Y Lee, Huaizhi Huang, Carolyn A Lumby, Jie Na, Lisa R Susswein, Maegan E Roberts, Megan L Marshall, Susan Hiraki, Holly LaDuca, Elizabeth Chao, Amal Yussuf, Tina Pesaran, Susan L Neuhausen, Christopher A Haiman, Peter Kraft, Sara Lindström, Julie R Palmer, Lauren R Teras, Celine M Vachon, Song Yao, Irene Ong, Katherine L Nathanson, Jeffrey N Weitzel, Nicholas Boddicker, Rohan Gnanaolivu, Eric C Polley, Georges Mer, Gaofeng Cui, Rachid Karam, Marcy E Richardson, Susan M Domchek, Siddhartha Yadav, Kathleen S Hruska, Jill Dolinsky, S John Weroha, Steven N Hart, Jacques Simard, Jean-Yves Masson, Yuan-Ping Pang, Fergus J Couch
Pathogenic protein-truncating variants of RAD51C, which plays an integral role in promoting DNA damage repair, increase the risk of breast and ovarian cancer. A large number of RAD51C missense variants of uncertain significance (VUS) have been identified, but the effects of the majority of these variants on RAD51C function and cancer predisposition have not been established. Here, analysis of 173 missense variants by a homology-directed repair (HDR) assay in reconstituted RAD51C-/- cells identified 30 non-functional (deleterious) variants, including 18 in a hotspot within the ATP binding region...
May 30, 2023: Cancer Research