Nature genetics · 2026
Cancer treatment alters mutant selection in normal esophagus.
СтатьяНазвание и аннотация: Перевод в очереди
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Fowler Joanna C, Arbore Giuseppina, Sood Roshan K, Abnizova Irina, Albarello Luca, Pickering Oliver, Murai Kasumi, Banerjee Ujjwal, Brunon Salomé, Ong Swee Hoe, Cossu Andrea, Elmore Ugo, Puccetti Francesco, Fernandez-Antoran David, Tonon Giovanni, Dellabona Paolo, Rosati Riccardo, Hill Samuel Luke, Underwood Tim, Hall Benjamin A, Shorthouse David, Jones Philip H
Аннотация
Aging epithelial tissues, including the esophagus, are colonized by somatic mutant clones under strong competitive selection. The effect of cancer treatment on mutant selection in normal epithelium is unknown. We hypothesized that some mutant clones may be selectively expanded during treatment. To test this, we sequenced normal esophageal epithelium removed from 70 patients after therapy for esophageal cancer. Patients received either no treatment, combination chemotherapy (FLOT, ECX or EOX) or chemotherapy and radiation therapy (CROSS). Mutant TP53 and PPM1D clones were expanded in patients undergoing CROSS. In the group undergoing FLOT, there was increased selection for RAC1, NFE2L2 and MTOR mutations consistent with these mutants conferring 5-fluorouracil resilience in normal epithelium. Sequencing normal epithelia reveals treatment-specific selection of mutations and may identify genes implicated in cellular responses to therapy.