Gene

TYMS

thymidylate synthetase

Explore in graph →CI-GENE-00037654HGNC:12441 ENSG00000176890 NCBI 7298 CIViC Cancer geneApproved

Curated evidence

Clinical evidence (11)

CIViC items involving this gene, grouped by molecular profile and therapy, with native levels and directions. 50 items per page.

civicCuratedShowing 1–11 of 11 evidence items · levels, directions and significance as curated at the source; each row links to its CIViC record.

Therapy	Cancer	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
TYMS 3TRP/3TRP genotype1
Fluorouracil + IrinotecanCombination	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	B	Supports

Cohorts

Alteration frequency by cohort (1)

Frequency = cases affected / cases profiled within one cohort. Cohorts are never pooled.

gdcObserved1 cohort row · frequency = affected / profiled, as published by each cohort; cohorts are not pooled. Hover a row badge for its release.

Cohort	Mapped cancer	Alteration	Affected (n)	Profiled (n)	Frequency (%)	Rank in cohort	Source
Lymphoid Neoplasm Diffuse Large B-cell Lymphoma TCGA-DLBC	Diffuse Large B-Cell LymphomaCURATED_BROADER

Literature

Linked publications (8)

25 per page, newest first.

pubmedPublishedShowing 1–8 of 8 publications · bibliographic data as recorded by PubMed; abstracts are not reproduced.

UGT1A and TYMS genetic variants predict toxicity and response of colorectal cancer patients treated with first-line irinotecan and fluorouracil combination therapy.
· Br J Cancer · 2010 · PMID 20628391 · validated civic_curation pubmed
Thymidylate synthase expression as a predictive biomarker of pemetrexed sensitivity in advanced non-small cell lung cancer.
· BMC Pulm Med · 2015 · PMID 26502926 · validated civic_curation pubmed
Thymidylate synthase gene copy number as a predictive marker for response to pemetrexed treatment of lung adenocarcinoma.
· Anticancer Res · 2013 · PMID 23645741 · validated civic_curation pubmed
Thymidylate synthase and dihydrofolate reductase expression in non-small cell lung carcinoma: the association with treatment efficacy of pemetrexed.
· Lung Cancer · 2011 · PMID 21367480

TYMS Amplification3
5-Fluorouracil/Salicylic Acid Topical Solution	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	B	Supports Resistance	3	submitted	EID12097 Genomic DNA from liver metastases of four different colorectal cancer patients who had previously undergone 5-FU-based adjuvant chemotherapy was evaluated using digital karyotyping. TYMS amplification… (full text at CIViC) PMID 14970324 · Wang et al., 2004 · Open in CIViC	civic
〃	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	B	Supports Resistance	3	submitted	EID12098 The TYMS DNA copy number was analyzed in 111 patient samples, divided into two groups: those exposed to 5-FU (n = 62) and those not exposed to 5-FU (n = 49). It was found that the 5-FU exposed group h… (full text at CIViC) PMID 20727737 · Watson et al., 2010 · Open in CIViC	civic
Pemetrexed	Lung Adenocarcinoma	Predictive	B	Supports Resistance	3	accepted	EID903 TYMS copy number was lower in clinical samples responding to pemetrexed in combination with platinum (n=25). The same was found in 17 cell lines. PMID 23645741 · Kasai et al., 2013 · Open in CIViC	civic

TYMS Amplification3

5-Fluorouracil/Salicylic Acid Topical Solution

Malignant Colorectal NeoplasmCURATED_BROADER

Predictive

Supports Resistance

submitted

EID12097

Genomic DNA from liver metastases of four different colorectal cancer patients who had previously undergone 5-FU-based adjuvant chemotherapy was evaluated using digital karyotyping. TYMS amplification… (full text at CIViC)

PMID 14970324 · Wang et al., 2004 · Open in CIViC

civic

〃

Malignant Colorectal NeoplasmCURATED_BROADER

Predictive

Supports Resistance

submitted

EID12098

The TYMS DNA copy number was analyzed in 111 patient samples, divided into two groups: those exposed to 5-FU (n = 62) and those not exposed to 5-FU (n = 49). It was found that the 5-FU exposed group h… (full text at CIViC)

PMID 20727737 · Watson et al., 2010 · Open in CIViC

civic

Pemetrexed

Lung Adenocarcinoma

Predictive

Supports Resistance

accepted

EID903

TYMS copy number was lower in clinical samples responding to pemetrexed in combination with platinum (n=25). The same was found in 17 cell lines.

PMID 23645741 · Kasai et al., 2013 · Open in CIViC

civic

TYMS Decreased RNA expression1
Fluorouracil	Malignant Colorectal NeoplasmCURATED_BROADER	Predictive	D	Supports Sensitivity Response	4	submitted	EID13313 Reduced TYMS expression by shRNA increased fluorouracil cytotoxicity in HCT-116, HT-29, and SW620 colorectal cancer cells, with approximately 3- to 8-fold enhancement of drug sensitivity. PMID 21449674 · Muhale et al., 2011 · Open in CIViC	civic

TYMS Decreased RNA expression1

Fluorouracil

Malignant Colorectal NeoplasmCURATED_BROADER

Predictive

Supports Sensitivity Response

submitted

EID13313

Reduced TYMS expression by shRNA increased fluorouracil cytotoxicity in HCT-116, HT-29, and SW620 colorectal cancer cells, with approximately 3- to 8-fold enhancement of drug sensitivity.

PMID 21449674 · Muhale et al., 2011 · Open in CIViC

civic

TYMS Overexpression3
Pemetrexed	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	B	Supports Resistance	3	accepted	EID832 mRNA expression of thymidylate synthase (TYMS) in 62 NSCLC patients correlated with response rate to pemetrexed mono- or combination therapy. Response rate with low TYMS expression was 0.29 compared w… (full text at CIViC) PMID 26502926 · Chamizo et al., 2015 · Open in CIViC	civic
〃	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	B	Supports Resistance	3	accepted	EID922 mRNA levels of TYMS, DHFR and GARFT were assessed (rt-PCR) in 50 patient samples of NSCLC. TYMS mRNA levels were lower in responders compared to non-responders to pemetrexed (1.671 ± 0.844 versus 5.97… (full text at CIViC) PMID 23060591 · Shimizu et al., 2012 · Open in CIViC	civic
Raltitrexed	Gastric Adenocarcinoma	Predictive	B	Supports Resistance	2	accepted	EID929 In 125 gastric tumors, plasma and tissue mRNA levels of TYMS were lower in the raltitrexed sensitive group compared to the resistant group (p = 0.007 and 0.013, respectively). PMID 22422354 · Shen et al., 2012 · Open in CIViC	civic

TYMS Overexpression3

Pemetrexed

Lung Non-Small Cell CarcinomaCURATED_BROADER

Predictive

Supports Resistance

accepted

EID832

mRNA expression of thymidylate synthase (TYMS) in 62 NSCLC patients correlated with response rate to pemetrexed mono- or combination therapy. Response rate with low TYMS expression was 0.29 compared w… (full text at CIViC)

PMID 26502926 · Chamizo et al., 2015 · Open in CIViC

civic

〃

Lung Non-Small Cell CarcinomaCURATED_BROADER

Predictive

Supports Resistance

accepted

EID922

mRNA levels of TYMS, DHFR and GARFT were assessed (rt-PCR) in 50 patient samples of NSCLC. TYMS mRNA levels were lower in responders compared to non-responders to pemetrexed (1.671 ± 0.844 versus 5.97… (full text at CIViC)

PMID 23060591 · Shimizu et al., 2012 · Open in CIViC

civic

Raltitrexed

Gastric Adenocarcinoma

Predictive

Supports Resistance

accepted

EID929

In 125 gastric tumors, plasma and tissue mRNA levels of TYMS were lower in the raltitrexed sensitive group compared to the resistant group (p = 0.007 and 0.013, respectively).

PMID 22422354 · Shen et al., 2012 · Open in CIViC

civic

TYMS RS347430331
Methotrexate	Malignant NeoplasmALIAS	Predictive	B	Supports Adverse Response	3	accepted	EID1843 499 children from ALL trials treated with methotrexate were genotyped for 8 SNPs in 5 genes. The TYMS rs34743033 tandem repeat polymorphism was the only significant predictor of stomatitis in a multip… (full text at CIViC) PMID 23652803 · Radtke et al., 2013 · Open in CIViC	civic

TYMS RS347430331

Methotrexate

Malignant NeoplasmALIAS

Predictive

Supports Adverse Response

accepted

EID1843

499 children from ALL trials treated with methotrexate were genotyped for 8 SNPs in 5 genes. The TYMS rs34743033 tandem repeat polymorphism was the only significant predictor of stomatitis in a multip… (full text at CIViC)

PMID 23652803 · Radtke et al., 2013 · Open in CIViC

civic

TYMS Underexpression2
Pemetrexed	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	B	Supports Sensitivity Response	3	accepted	EID907 49 tumor specimens from 268 NSCLC patients treated with pemetrexed were evaluated for expression of TYMS and DHFR by IHC and compared to treatment outcomes. Patients with low TS (≤150) expression had … (full text at CIViC) PMID 21367480 · Chen et al., 2011 · Open in CIViC	civic
〃	Malignant Prostate Neoplasm	Predictive	C	Supports Sensitivity Response	2	accepted	EID908 Case report of a patient with metastatic prostate cancer and underexpression of TYMS who showed a nonspecified response to pemetrexed for at least 4 months. PMID 24782778 · Russell et al., 2014 · Open in CIViC	civic

TYMS Underexpression2

Pemetrexed

Lung Non-Small Cell CarcinomaCURATED_BROADER

Predictive

Supports Sensitivity Response

accepted

EID907

49 tumor specimens from 268 NSCLC patients treated with pemetrexed were evaluated for expression of TYMS and DHFR by IHC and compared to treatment outcomes. Patients with low TS (≤150) expression had … (full text at CIViC)

PMID 21367480 · Chen et al., 2011 · Open in CIViC

civic

〃

Malignant Prostate Neoplasm

Predictive

Supports Sensitivity Response

accepted

EID908

Case report of a patient with metastatic prostate cancer and underexpression of TYMS who showed a nonspecified response to pemetrexed for at least 4 months.

PMID 24782778 · Russell et al., 2014 · Open in CIViC

civic