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Mutational_burden_in_oesophagus_following_chemotherapy_and_radiotherapy_treatment_WGS

We wish to assess the changes in signature and mutational burden in patients who have undergone either chemotherapy or chemotherapy + radiotherapy. Using duplex sequencing will assess the mutational landscape in oesophageal epithelia in patients who have undergone these treatment regimes.

Type: Cancer Genomics
Archive: European Genome-phenome Archive (EGA)

1 Dataset 1 Publication

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Dataset ID	Description	Technology	Samples
EGAD00001011181	Ageing epithelial tissues, including the esophagus, are progressively colonized by somatic mutant clones, some carrying mutations linked to cancer. However, whether normal epithelial mutational landscapes that evolve over decades can be altered by short term interventions such as cancer treatment is not known. Here we sequenced normal esophageal epithelium removed from patients after 5-8 weeks of therapy for esophageal cancer. Some patients had no prior treatment (NT), while others had 8 weeks of 5 Fluorouracil (5-FU) containing chemotherapy (FLOT) or 4 weeks of chemotherapy and radiation directed at the tumor (CROSS). Despite the brief duration of therapy, we observed treatment specific differences in the selection of mutant clones. The median size of mutant TP53 and PPM1D clones in the CROSS group was double that in the other groups. Mutants of the tumor suppressor SPOP were selected in CROSS but not FLOT or NT patients. In FLOT patients we found positive selection of activating MTOR mutations, consistent with the hypothesis that these mutants confer 5-FU resistance. Sequencing densely mutated normal epithelia after cancer reveals treatment specific selection of mutations with potential therapeutic impact.	Illumina NovaSeq 6000	56

Publications	Citations
Cancer treatment alters mutant selection in normal esophagus. Fowler JC, Arbore G, Sood RK, Abnizova I, Albarello L, Pickering O, Murai K, Banerjee U, Brunon S, Ong SH, Cossu A, Elmore U, Puccetti F, Fernandez-Antoran D, Tonon G, Dellabona P, Rosati R, Hill SL, Underwood T, Hall BA, Shorthouse D, Jones PH. Nat Genet 58: 2026 2566-2578	0