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

Dominic Schaerer; Tanja K. Froehlich; Seid Hamzic; Steven M. Offer; Robert B. Diasio; Markus Joerger; Ursula Amstutz; Carlo R. Largiader

doi:10.3390/jpm10040181

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

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

Dominic Schaerer, Tanja K. Froehlich, Seid Hamzic, Steven M. Offer, Robert B. Diasio, Markus Joerger, Ursula Amstutz and Carlo R. Largiader

Journal of personalized medicine, Vol.10(4), pp.1-13

10/19/2020

DOI: 10.3390/jpm10040181

PMCID: PMC7712088

PMID: 33086767

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Abstract

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.

General & Internal Medicine

Health Care Sciences & Services

Life Sciences & Biomedicine

Medicine, General & Internal

Science & Technology

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Title: Subtitle: A Novel Nomenclature for Repeat Motifs in the Thymidylate Synthase Enhancer Region and Its Relevance for Pharmacogenetic Studies
Creators: Dominic Schaerer - University Hospital of Bern
Tanja K. Froehlich - University Hospital of Bern
Seid Hamzic - University Hospital of Bern
Steven M. Offer - Mayo Clinic
Robert B. Diasio - Mayo Clinic
Markus Joerger - University of St. Gallen
Ursula Amstutz - University Hospital of Bern
Carlo R. Largiader - University Hospital of Bern
Resource Type: Journal article
Publication Details: Journal of personalized medicine, Vol.10(4), pp.1-13
Publisher: Mdpi
DOI: 10.3390/jpm10040181
PMID: 33086767
PMCID: PMC7712088
ISSN: 2075-4426
eISSN: 2075-4426
Number of pages: 13
Grant note: 163205 / Swiss National Science Foundation; Swiss National Science Foundation (SNSF)
Language: English
Date published: 10/19/2020
Academic Unit: Pathology
Record Identifier: 9984618512302771

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