ESR1 and melanoma: In an attempt to characterize genes that may have contributed to 5-FU resistance, we performed a dN/dS analysis in which all single-nucleotide mutations and small insertions and deletions (INDELS) were included, but revealed no significantly mutated genes in contrast to resistance to hormonal therapies (e.g., ESR1 for breast and AR for prostate17,31) and targeted treatments (e.g., secondary BRAF mutations for melanoma treated with vemurafenib32 and secondary EGFR mutations treated with EGFR inhibitors33).