{ "labelLang" : "hun", "responseDate" : "2024-03-29 02:23", "content" : { "otype" : "JournalArticle", "mtid" : 3360372, "status" : "VALIDATED", "published" : true, "comment" : "These authors contributed equally: Lőrinc Pongor and Giulia Bottai\nMTA TTK Lendület Cancer Biomarker Research Group, Institute of Enzymology, Budapest, H-1117, Hungary \n 2nd Department of Pediatrics, Semmelweis University, Budapest, H-1094, Hungary \n Oncology Experimental Therapeutics, Humanitas Clinical and Research Institute, Rozzano, Milan, 20089, Italy \n Breast Medical Oncology, Yale Cancer Center, Yale School of Medicine, New Haven, CT 06520, United States \n Institute of Pathology, Charité University Hospital, Berlin, 10117, Germany \n Cited By :13 \n Export Date: 25 March 2020 \n CODEN: BJCAA \n Correspondence Address: Santarpia, L.; Oncology Experimental Therapeutics, Humanitas Clinical and Research Institute, RozzanoItaly; email: liberosantarpia@yahoo.it\nMTA TTK Lendület Cancer Biomarker Research Group, Institute of Enzymology, Budapest, H-1117, Hungary \n 2nd Department of Pediatrics, Semmelweis University, Budapest, H-1094, Hungary \n Oncology Experimental Therapeutics, Humanitas Clinical and Research Institute, Rozzano, Milan, 20089, Italy \n Breast Medical Oncology, Yale Cancer Center, Yale School of Medicine, New Haven, CT 06520, United States \n Institute of Pathology, Charité University Hospital, Berlin, 10117, Germany \n Cited By :13 \n Export Date: 26 March 2020 \n CODEN: BJCAA \n Correspondence Address: Santarpia, L.; Oncology Experimental Therapeutics, Humanitas Clinical and Research Institute, RozzanoItaly; email: liberosantarpia@yahoo.it\nMTA TTK Lendület Cancer Biomarker Research Group, Institute of Enzymology, Budapest, H-1117, Hungary \n 2nd Department of Pediatrics, Semmelweis University, Budapest, H-1094, Hungary \n Oncology Experimental Therapeutics, Humanitas Clinical and Research Institute, Rozzano, Milan, 20089, Italy \n Breast Medical Oncology, Yale Cancer Center, Yale School of Medicine, New Haven, CT 06520, United States \n Institute of Pathology, Charité University Hospital, Berlin, 10117, Germany \n Cited By :13 \n Export Date: 22 April 2020 \n CODEN: BJCAA \n Correspondence Address: Santarpia, L.; Oncology Experimental Therapeutics, Humanitas Clinical and Research Institute, RozzanoItaly; email: liberosantarpia@yahoo.it\nMTA TTK Lendület Cancer Biomarker Research Group, Institute of Enzymology, Budapest, H-1117, Hungary \n 2nd Department of Pediatrics, Semmelweis University, Budapest, H-1094, Hungary \n Oncology Experimental Therapeutics, Humanitas Clinical and Research Institute, Rozzano, Milan, 20089, Italy \n Breast Medical Oncology, Yale Cancer Center, Yale School of Medicine, New Haven, CT 06520, United States \n Institute of Pathology, Charité University Hospital, Berlin, 10117, Germany \n Cited By :15 \n Export Date: 9 October 2020 \n CODEN: BJCAA \n Correspondence Address: Santarpia, L.; Oncology Experimental Therapeutics, Humanitas Clinical and Research Institute, RozzanoItaly; email: liberosantarpia@yahoo.it\nFunding Agency and Grant Number: Fondazione Italiana Ricerca sul Cancro (FIRC fellowship)Associazione Italiana per la Ricerca sul Cancro (AIRC) [18328]; National Research, Development and Innovation Office of Hungary [NVKP_16-1-2016-0037]; Breast Cancer Research Foundation; NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Center for Advancing Translational Sciences (NCATS) [UL1TR001863, UL1TR001863, UL1TR001863, UL1TR001863, UL1TR001863, UL1TR001863, UL1TR001863, UL1TR001863] Funding Source: NIH RePORTER\n Funding text: This study was supported by Fondazione Italiana Ricerca sul Cancro (FIRC fellowship 18328 to G.B.), the NVKP_16-1-2016-0037 grant of the National Research, Development and Innovation Office of Hungary (to B.G.), and Breast Cancer Research Foundation (to L.P.).\nMTA TTK Lendület Cancer Biomarker Research Group, Institute of Enzymology, Budapest, H-1117, Hungary \n 2nd Department of Pediatrics, Semmelweis University, Budapest, H-1094, Hungary \n Oncology Experimental Therapeutics, Humanitas Clinical and Research Institute, Rozzano, Milan, 20089, Italy \n Breast Medical Oncology, Yale Cancer Center, Yale School of Medicine, New Haven, CT 06520, United States \n Institute of Pathology, Charité University Hospital, Berlin, 10117, Germany \n Cited By :16 \n Export Date: 20 November 2020 \n CODEN: BJCAA \n Correspondence Address: Santarpia, L.; 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Oncology Experimental Therapeutics, Italy; email: liberosantarpia@yahoo.it\nMTA TTK Lendület Cancer Biomarker Research Group, Institute of Enzymology, Budapest, H-1117, Hungary \n 2nd Department of Pediatrics, Semmelweis University, Budapest, H-1094, Hungary \n Oncology Experimental Therapeutics, Humanitas Clinical and Research Institute, Rozzano, Milan, 20089, Italy \n Breast Medical Oncology, Yale Cancer Center, Yale School of Medicine, New Haven, CT 06520, United States \n Institute of Pathology, Charité University Hospital, Berlin, 10117, Germany \n Cited By :18 \n Export Date: 7 May 2021 \n CODEN: BJCAA \n Correspondence Address: Santarpia, L.; Oncology Experimental Therapeutics, Italy; email: liberosantarpia@yahoo.it\nMTA TTK Lendület Cancer Biomarker Research Group, Institute of Enzymology, Budapest, H-1117, Hungary \n 2nd Department of Pediatrics, Semmelweis University, Budapest, H-1094, Hungary \n Oncology Experimental Therapeutics, Humanitas Clinical and Research Institute, Rozzano, Milan, 20089, Italy \n Breast Medical Oncology, Yale Cancer Center, Yale School of Medicine, New Haven, CT 06520, United States \n Institute of Pathology, Charité University Hospital, Berlin, 10117, Germany \n Cited By :19 \n Export Date: 2 July 2021 \n CODEN: BJCAA \n Correspondence Address: Santarpia, L.; Oncology Experimental Therapeutics, Italy; email: liberosantarpia@yahoo.it\nMTA TTK Lendület Cancer Biomarker Research Group, Institute of Enzymology, Budapest, H-1117, Hungary \n 2nd Department of Pediatrics, Semmelweis University, Budapest, H-1094, Hungary \n Oncology Experimental Therapeutics, Humanitas Clinical and Research Institute, Rozzano, Milan, 20089, Italy \n Breast Medical Oncology, Yale Cancer Center, Yale School of Medicine, New Haven, CT 06520, United States \n Institute of Pathology, Charité University Hospital, Berlin, 10117, Germany \n Cited By :19 \n Export Date: 6 August 2021 \n CODEN: BJCAA \n Correspondence Address: Santarpia, L.; Oncology Experimental Therapeutics, Italy; email: liberosantarpia@yahoo.it\nMTA TTK Lendület Cancer Biomarker Research Group, Institute of Enzymology, Budapest, H-1117, Hungary \n 2nd Department of Pediatrics, Semmelweis University, Budapest, H-1094, Hungary \n Oncology Experimental Therapeutics, Humanitas Clinical and Research Institute, Rozzano, Milan, 20089, Italy \n Breast Medical Oncology, Yale Cancer Center, Yale School of Medicine, New Haven, CT 06520, United States \n Institute of Pathology, Charité University Hospital, Berlin, 10117, Germany \n Cited By :19 \n Export Date: 12 August 2021 \n CODEN: BJCAA \n Correspondence Address: Santarpia, L.; 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Methods: In this study, we integrated somatic mutations, gene expression and clinical data from 930 breast cancer patients included in the TCGA database. Genes associated with single mutations in molecular breast cancer subtypes were identified by the Mann-Whitney U-test and their prognostic value was evaluated by Kaplan-Meier and Cox regression analyses. Results were confirmed using gene expression profiles from the Metabric data set (n = 1988) and whole-genome sequencing data from the TCGA cohort (n = 117). Results: The overall mutation rate in coding and non-coding regions were significantly higher in ER-negative/HER2-negative tumours (P = 2.8E–03 and P = 2.4E–07, respectively). Recurrent sequence variations were identified in non-coding regulatory regions of several cancer-associated genes, including NBPF1, PIK3CA and TP53. After multivariate regression analysis, gene signatures associated with three coding mutations (CDH1, MAP3K1 and TP53) and two non-coding variants (CRTC3 and STAG2) in cancer-related genes predicted prognosis in ER-positive/HER2-negative tumours. Conclusions: These findings demonstrate that sequence alterations influence gene expression and oncogenic pathways, possibly affecting the outcome of breast cancer patients. 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