Prognostic Significance of the Loss of Heterozygosity of KRAS in Early-Stage Lung Adenocarcinoma.

Autor:	Khadse A; Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; Faculty of Technology, Natural Sciences and Maritime Sciences, Department of Natural Sciences and Environmental Health, University of South-Eastern Norway, Bø i Telemark, Norway., Haakensen VD; Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; Department of Oncology, Oslo University Hospital, Oslo, Norway., Silwal-Pandit L; Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway., Hamfjord J; Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; Department of Oncology, Oslo University Hospital, Oslo, Norway., Micke P; Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden., Botling J; Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden., Brustugun OT; Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; Section of Oncology, Drammen Hospital, Vestre Viken Hospital Trust, Drammen, Norway., Lingjærde OC; Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; Centre for Bioinformatics, Department of Informatics, University of Oslo, Oslo, Norway., Helland Å; Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; Department of Oncology, Oslo University Hospital, Oslo, Norway.; Department of Clinical Medicine, University of Oslo, Oslo, Norway., Kure EH; Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; Faculty of Technology, Natural Sciences and Maritime Sciences, Department of Natural Sciences and Environmental Health, University of South-Eastern Norway, Bø i Telemark, Norway.
Jazyk:	angličtina
Zdroj:	Frontiers in oncology [Front Oncol] 2022 Apr 29; Vol. 12, pp. 873532. Date of Electronic Publication: 2022 Apr 29 (Print Publication: 2022).
DOI:	10.3389/fonc.2022.873532
Abstrakt:	Lung cancer is a common disease with a poor prognosis. Genomic alterations involving the KRAS gene are common in lung carcinomas, although much is unknown about how different mutations, deletions, and expressions influence the disease course. The first approval of a KRAS -directed inhibitor was recently approved by the FDA. Mutations in the KRAS gene have been associated with poor prognosis for lung adenocarcinomas, but implications of the loss of heterozygosity (LOH) of KRAS have not been investigated. In this study, we have assessed the LOH of KRAS in early-stage lung adenocarcinoma by analyzing DNA copy number profiles and have investigated the effect on patient outcome in association with mRNA expression and somatic hotspot mutations. KRAS mutation was present in 36% of cases and was associated with elevated mRNA expression. LOH in KRAS was associated with a favorable prognosis, more prominently in KRAS mutated than in wild-type patients. The presence of both LOH and mutation in KRAS conferred a better prognosis than KRAS mutation alone. For wild-type tumors, no difference in prognosis was observed between patients with and without LOH in KRAS . Our study indicates that LOH in KRAS is an independent prognostic factor that may refine the existing prognostic groups of lung adenocarcinomas. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Khadse, Haakensen, Silwal-Pandit, Hamfjord, Micke, Botling, Brustugun, Lingjærde, Helland and Kure.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu