دورية أكاديمية
Extensive genomic analysis in patients with KRAS -mutated solid tumors shows high frequencies of concurrent alterations and potential targets but has limited clinical impact.
| العنوان: | Extensive genomic analysis in patients with KRAS -mutated solid tumors shows high frequencies of concurrent alterations and potential targets but has limited clinical impact. |
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| المؤلفون: | Jacobsen IC; Phase 1 Unit, Department of Oncology, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark., Spanggaard I; Phase 1 Unit, Department of Oncology, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark., Højgaard M; Phase 1 Unit, Department of Oncology, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark., Belcaid L; Phase 1 Unit, Department of Oncology, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark., Qvortrup C; Phase 1 Unit, Department of Oncology, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark., Yde CW; Center for Genomic Medicine, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark., Schmidt AY; Center for Genomic Medicine, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark., Nielsen FC; Center for Genomic Medicine, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark., Willemoe GL; Department of Pathology, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark., Dam MS; Department of Diagnostic Radiology, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark., Lassen U; Phase 1 Unit, Department of Oncology, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark., Staal Rohrberg K; Phase 1 Unit, Department of Oncology, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark. |
| المصدر: | Acta oncologica (Stockholm, Sweden) [Acta Oncol] 2022 Dec; Vol. 61 (12), pp. 1499-1506. Date of Electronic Publication: 2022 Dec 18. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Medical Journals Sweden AB Country of Publication: England NLM ID: 8709065 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1651-226X (Electronic) Linking ISSN: 0284186X NLM ISO Abbreviation: Acta Oncol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2024- : [Uppsala, Sweden] : Medical Journals Sweden AB Original Publication: Stockholm, Sweden : Acta Oncologica, [1987- |
| مواضيع طبية MeSH: | Carcinoma, Non-Small-Cell Lung*/genetics , Lung Neoplasms*/genetics, Humans ; Proto-Oncogene Proteins p21(ras)/genetics ; Prospective Studies ; Mutation ; Genomics ; Codon |
| مستخلص: | Background: This study aimed to investigate the distribution and frequency of concurrent alterations in different cancers across KRAS subtypes and in different KRAS subtypes across cancers, and to identify potentially actionable targets and patients who received targeted treatment matched to their genomic profile (GP). Materials and Methods: In this descriptive and single-center study, we included 188 patients with solid tumors harboring KRAS mutations in codon 12, 13, 61, 117, or 146, referred to the Phase 1 Unit, Rigshospitalet, Copenhagen, Denmark from mid-2016 to 2020. Genomic co-alterations were detected with whole-exome sequencing, RNA sequencing, SNP array, and mRNA expression array on fresh biopsies. The study is part of the Copenhagen Prospective Personalized Oncology study (NCT02290522). Results: The majority of patients had colorectal cancer (60.1%), non-small cell lung cancer (11.2%), or pancreatic cancer (10.6%). Most tumors were KRAS -mutated in codon 12 or 13 (93.7%) including G12D (27.1%), G12V (26.6%), G12C (11.7%), and G13D (11.2%). A total of 175 different co-alterations were found, most frequently pathogenic APC and TP53 mutations (55.9% and 46.4%, respectively) and high expression of CEACAM5 (73.4%). Different cancers and KRAS subtypes showed different patterns of co-alterations, and 157 tumors (83.5%) had potentially actionable targets with varying evidence of targetability (assessed using ESMO Scale for Clinical Actionability of molecular Targets). Of the 188 patients included in the study, 15 (7.4%) received treatment matched to their GP (e.g., immunotherapy and synthetic lethality drugs), of whom one had objective partial response according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Conclusion: Performing extensive genomic analysis in patients with known KRAS -mutated solid tumors may contribute with information to the genomic landscape of cancers and identify targets for immunotherapy or synthetic lethality drugs, but currently appears to have overall limited clinical impact, as few patients received targeted therapy matched to their GP. |
| فهرسة مساهمة: | Keywords: KRAS mutation; actionable targets; genomic alterations; personalized medicine |
| سلسلة جزيئية: | ClinicalTrials.gov NCT02290522 |
| المشرفين على المادة: | EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras)) 0 (Codon) 0 (KRAS protein, human) |
| تواريخ الأحداث: | Date Created: 20221219 Date Completed: 20230118 Latest Revision: 20230118 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1080/0284186X.2022.2156809 |
| PMID: | 36529989 |
| قاعدة البيانات: | MEDLINE |
PDF full text from Publisher | تدمد: | 1651-226X |
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| DOI: | 10.1080/0284186X.2022.2156809 |