title: Long Survival and Severe Toxicity Under 5-Fluorouracil-Based Therapy in a Patient With Colorectal Cancer Who Harbors a Germline Codon-Stop Mutation in TYMS.
abstract: We report the first clinical description of a patient with cancer with a heterozygous germline codon-stop mutation in the TYMS gene. The mutation g.657795_657826del, c.53_84del (NM_001071.2), p.Gln18Argfs*42 causes loss of function of one of the TYMS alleles, resulting in a truncated protein. This gene codifies for the target enzyme of 5-fluorouracil (5-FU), the basic treatment in colorectal cancer. The patient, diagnosed with metastatic colorectal cancer, had diarrhea and neutropenia grade 4 and mucositis and neurological toxicity grade 3 under 5-FU-based therapy and exceeded by more than 50% the average survival after metastasectomy. On the basis of the patient's characteristics and the key role of TYMS in 5-FU activity, we hypothesize that this mutation may contribute to the drug response and toxicities suffered by the patient.
authors.affiliation: Genomic Medicine Group, CIBERER, University of Santiago de Compostela, Santiago de Compostela, Spain. Electronic address: emilia.balboa@usc.es.
authors.forename: Emilia
authors.initials: E
authors.lastname: Balboa-Beltrán
authors.affiliation: Hospital Pharmacy Service, University Hospital Complex of Santiago de Compostela (CHUS), Santiago de Compostela, Spain.
authors.forename: Goretti
authors.initials: G
authors.lastname: Duran
authors.affiliation: Hospital Pharmacy Service, University Hospital Complex of Santiago de Compostela (CHUS), Santiago de Compostela, Spain.
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Lamas
authors.affiliation: Genomic Medicine Group, CIBERER, University of Santiago de Compostela, Santiago de Compostela, Spain; Galician Public Foundation for Genomic Medicine, SERGAS, Santiago de Compostela, Spain; Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, KSA.
authors.forename: Angel
authors.initials: A
authors.lastname: Carracedo
authors.affiliation: Galician Public Foundation for Genomic Medicine, SERGAS, Santiago de Compostela, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Barros
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects* / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003967:Diarrhea / Q000139:chemically induced; D005472:Fluorouracil / Q000009:adverse effects* / Q000627:therapeutic use; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D052016:Mucositis / Q000139:chemically induced; D011110:Polymorphism, Genetic; D013940:Thymidylate Synthase / Q000235:genetics*
chemical_list: D000964:Antimetabolites, Antineoplastic; D013940:Thymidylate Synthase; D005472:Fluorouracil