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In terms of genomic instability, gain-of-function mutations of proto-oncogenes (e.g., KRAS, 10 BRAF, 11 EGFR 12 and ERBB2 13 ), loss-of-function mutations of tumor suppressor genes (e.g., TP53, 14 PTEN 15 and APC 16 ), and defects in DNA damage repair genes (e.g., BRCA1/2, 17 MSH2 and MLH1 18 ) have been reported to drive tumorigenesis in a number of cancer types

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