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We designed a panel of 558 genes with pharmacogenomics records related to 5-fluorouracil resistance, genes important for sensitivity to other frequently used drugs, major oncodrivers, and actionable genes. We performed a target enrichment sequencing of DNA from tumors and matched blood samples of patients, and compared the results with patient prognosis stratified by systemic adjuvant chemotherapy.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The median number of detected variants per tumor sample was 18.5 with 4 classified as having a high predicted functional effect and 14.5 moderate effect. <jats:italic>APC, TP53<\/jats:italic>, and <jats:italic>KRAS<\/jats:italic> were the most frequent mutated genes (64%, 59%, and 42% of mutated samples, respectively) followed by <jats:italic>FAT4<\/jats:italic> (23%), <jats:italic>FBXW7<\/jats:italic>, and <jats:italic>PIK3CA<\/jats:italic> (16% for both). Patients with advanced stage III had more frequently <jats:italic>APC<\/jats:italic>, <jats:italic>TP53<\/jats:italic>, or <jats:italic>KRAS<\/jats:italic> mutations than those in stages I or II. <jats:italic>KRAS<\/jats:italic> mutation counts followed an increasing trend with grade (G1\u2009&lt;\u2009G2\u2009&lt;\u2009G3). The response to adjuvant therapy was worse in carriers of frameshift mutations in <jats:italic>APC<\/jats:italic> or 12D variant in <jats:italic>KRAS<\/jats:italic>, but none of these oncodrivers had prognostic value. Carriage of somatic mutations in any of the genes <jats:italic>ABCA13, ANK2, COL7A1, NAV3<\/jats:italic>, or<jats:italic> UNC80<\/jats:italic> had prognostic relevance for worse overall survival (OS) of all patients. In contrast, mutations in <jats:italic>FLG, GLI3<\/jats:italic>, or <jats:italic>UNC80<\/jats:italic> were prognostic in the same direction for patients untreated, and mutations in <jats:italic>COL6A3, LRP1B, NAV3, RYR1, RYR3, TCHH<\/jats:italic>, or <jats:italic>TENM4<\/jats:italic> for patients treated with adjuvant therapy. The first association was externally validated. From all germline variants with high or moderate predicted functional effects (median 326 per patient), &gt;\u20095% frequency and positive Manhattan plot based on 3-year RFS, rs72753407 in <jats:italic>NFACS<\/jats:italic>, rs34621071 in <jats:italic>ERBB4<\/jats:italic>, and rs2444274 in <jats:italic>RIF1<\/jats:italic> were significantly associated with RFS, OS or both.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>The present study identified several putative somatic and germline genetic events with prognostic potential for colorectal cancer that should undergo functional characterization.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s40246-024-00644-2","type":"journal-article","created":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T10:01:44Z","timestamp":1721383304000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Targeted panel sequencing of pharmacogenes and oncodrivers in colorectal cancer patients reveals genes with prognostic significance"],"prefix":"10.1186","volume":"18","author":[{"given":"Lucie","family":"Heczko","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e1clav","family":"Li\u0161ka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ond\u0159ej","family":"Vy\u010d\u00edtal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ond\u0159ej","family":"Fiala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"\u0160\u016fsov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0695-0552","authenticated-orcid":false,"given":"Viktor","family":"Hlav\u00e1\u010d","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4294-6799","authenticated-orcid":false,"given":"Pavel","family":"Sou\u010dek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,19]]},"reference":[{"issue":"3","key":"644_CR1","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. 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The study protocol was approved by the Ethical Commission of the Faculty of Medicine and University Hospital in Pilsen (approval no. NT12025-4 of 16 September 2010). All patients provided their informed consent with the study participation.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Ond\u0159ej Fiala received honoraria from Novartis, Janssen, Merck, BMS, MSD, Pierre Fabre, and Pfizer for consultations and lectures unrelated to this project. The rest of authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}],"article-number":"83"}}