biostudies-literatureChatila WKU.S. Department of Health & Human Services | NIH | National Cancer InstituteNCI NIH HHSU.S. Department of Health & Human Services | NIH | Center for Scientific ReviewNIGMS NIH HHS1646-1655https://www.ebi.ac.uk/biostudies/studies/S-EPMC9801308biostudies-literatureUnknown28(8)The incidence of rectal cancer is increasing in patients younger than 50 years. Locally advanced rectal cancer is still treated with neoadjuvant radiation, chemotherapy and surgery, but recent evidence suggests that patients with a complete response can avoid surgery permanently. To define correlates of response to neoadjuvant therapy, we analyzed genomic and transcriptomic profiles of 738 untreated rectal cancers. APC mutations were less frequent in the lower than in the middle and upper rectum, which could explain the more aggressive behavior of distal tumors. No somatic alterations had significant associations with response to neoadjuvant therapy in a treatment-agnostic manner, but KRAS mutations were associated with faster relapse in patients treated with neoadjuvant chemoradiation folNature medicineGenomic and transcriptomic determinants of response to neoadjuvant therapy in rectal cancer.PMC9801308T32 CA009501P30 CA008748R01 CA090559T32 GM132083K08 CA255574Ho YJShi QPelossof RDonoghue MTAWu FOmer DMRomesser PBYaeger RGarcia-Aguilar JWei IHSanchez-Vega FCercek ASmith JJChen CTSchultz NQu XGanesh KBerger MFLuthra AWidmar MKim JKWeiser MRGroves KIWalch HPappou EPDuygu Selcuklu SNash GMPaty PBChoi SHKhalil DNVakiani EChatila WKChow OSShia JKundra RMarco MRSolit DBfalseGenomic and transcriptomic determinants of response to neoadjuvant therapy in rectal cancer.The incidence of rectal cancer is increasing in patients younger than 50 years. Locally advanced rectal cancer is still treated with neoadjuvant radiation, chemotherapy and surgery, but recent evidence suggests that patients with a complete response can avoid surgery permanently. To define correlates of response to neoadjuvant therapy, we analyzed genomic and transcriptomic profiles of 738 untreated rectal cancers. APC mutations were less frequent in the lower than in the middle and upper rectum, which could explain the more aggressive behavior of distal tumors. No somatic alterations had significant associations with response to neoadjuvant therapy in a treatment-agnostic manner, but KRAS mutations were associated with faster relapse in patients treated with neoadjuvant chemoradiation fol2022-01-01T00:00:00Z2022 Aug2026-05-27T20:48:45.465Z2025-02-19T04:45:22.578ZS-EPMC98013083597091910.1038/s41591-022-01930-z