A Novel Nomenclature for Repeat Motifs in the Thymidylate Synthase Enhancer Region and Its Relevance for Pharmacogenetic Studies.

Schaerer, Dominic; Froehlich, Tanja K.; Hamzic, Seid; Offer, Steven M.; Diasio, Robert B.; Joerger, Markus; Amstutz, Ursula; Largiadèr, Carlo R. (2020). A Novel Nomenclature for Repeat Motifs in the Thymidylate Synthase Enhancer Region and Its Relevance for Pharmacogenetic Studies. Journal of personalized medicine, 10(4) MDPI 10.3390/jpm10040181

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Inhibition of thymidylate synthase (TS) is the primary mode of action for 5-fluorouracil (5FU) chemotherapy. TS expression is modulated by a variable number of tandem repeats in the TS enhancer region (TSER) located upstream of the TS gene (TYMS). Variability in the TSER has been suggested to contribute to 5FU-induced adverse events. However, the precise genetic associations remain largely undefined due to high polymorphism and ambiguity in defining genotypes. To assess toxicity associations, we sequenced the TSER in 629 cancer patients treated with 5FU. Of the 13 alleles identified, few could be unambiguously named using current TSER-nomenclature. We devised a concise and unambiguous systematic naming approach for TSER-alleles that encompasses all known variants. After applying this comprehensive naming system to our data, we demonstrated that the number of upstream stimulatory factor (USF1-)binding sites in the TSER was significantly associated with gastrointestinal toxicity in 5FU treatment.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute of Clinical Chemistry

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Schärer, Dominic Manuel; Fröhlich, Tanja; Hamzic, Seid; Amstutz, Ursula and Largiadèr, Carlo Rodolfo

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2075-4426

Publisher:

MDPI

Language:

English

Submitter:

Karin Balmer

Date Deposited:

09 Nov 2020 08:34

Last Modified:

09 Nov 2020 08:34

Publisher DOI:

10.3390/jpm10040181

PubMed ID:

33086767

Uncontrolled Keywords:

5-fluorouracil adverse drug reactions capecitabine fluoropyrimidine thymidylate synthase thymidylate synthase enhancer region upstream stimulatory factor 1

BORIS DOI:

10.7892/boris.147775

URI:

https://boris.unibe.ch/id/eprint/147775

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