scholarly journals Mutation Analysis in the Coding Sequence of Thymidine Kinase 1 in Breast and Colorectal Cancer

2003 ◽  
Vol 18 (1) ◽  
pp. 1-6 ◽  
Author(s):  
S.I. Gilles ◽  
S. Romain ◽  
P. Casellas ◽  
L'h. Ouafik ◽  
F. Fina ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Thymidine Kinase ◽  
Phosphorylation Site ◽  
Normal Mucosa ◽  
Missense Mutations ◽  
Coding Region ◽  
Thymidine Kinase 1 ◽  
Atp Binding Site ◽  
Normal Tissues ◽  
Putative Phosphorylation Site

We report the first mutational study of thymidine kinase 1 (TK1) performed in human solid tumors. We sequenced cDNAs representing the complete coding region of TK1 in human breast (n=22) and colorectal (n=26) cancer. Codon 106 near the ATP binding site constantly differed (ATG → GTG; Met → Val) from the one deposited by Bradshaw and Deininger in the Genbank database (Accession number NM_003258). Silent polymorphisms at codon 11 (CCC → CCT; Pro → Pro) and codon 75 (GCG → GCA; Ala → Ala) were frequently detected in tumors as well as in normal tissues. In breast cancer the two polymorphisms were observed in 63.6% of the samples analyzed. No significant association could be found between polymorphisms and TK activity. In colorectal cancer the incidence of the two changes was 73.1% and 69.2%, respectively. Interestingly, one colon cancer with high cytosolic TK activity displayed two missense mutations located in and near the putative phosphorylation site by tyrosine kinase (s) (TAT → CAT; Tyr → His) and by cAMP-, cGMP-dependent protein kinase (TAC → TGC; Tyr → Cys), respectively; adjacent normal mucosa showed no mutation. This may open new avenues that imply TK1 activity in tumor cell proliferation.

The Effect of High CDC6 Levels on Predicting Poor Prognosis in Colorectal Cancer

Chemotherapy ◽  
2022 ◽  
pp. 1-10
Author(s):  
Cheng Yang ◽  
Na Xie ◽  
Zhifei Luo ◽  
Xiling Ruan ◽  
Yixin Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Protein Expression ◽  
Poor Prognosis ◽  
Cancer Metastasis ◽  
Mrna Level ◽  
Normal Mucosa ◽  
Tnm Stage ◽  
Expression Levels ◽  
Normal Tissues

<b><i>Introduction:</i></b> We investigated the function of cell division cycle 6 (CDC6) on the prognosis in colorectal carcinoma (CRC). <b><i>Methods:</i></b> CDC6 protein expression levels in 121 patients with colorectal cancer and adjacent normal mucosa were detected by immunohistochemistry. <b><i>Results:</i></b> Compared to adjacent normal tissues, CDC6 mRNA level was overexpressed in CRC tissues. Moreover, CDC6 protein levels were expressed up to 93.39% (113/121) in CRC tissues in the cell nucleus or cytoplasm. However, there were only 5.79% (7/121) in normal mucosal tissues with nuclear expression. CDC6 expression was significantly correlated with TNM stage and tumor metastasis. The 5-year survival rate was lower in the high CDC6 expression group than the low group. After silencing of CDC6 expression in SW620 cells, cell proliferation was slowed, the tumor clones were decreased, and the cell cycle was arrested in G1 phase. In multivariate analysis, increased CDC6 protein expression levels in colon cancer tissues were associated with cancer metastasis, TNM stage, and patient survival time. <b><i>Conclusion:</i></b> CDC6 is highly expressed in CRC, and downregulation of CDC6 can slow the growth of CRC cells in vitro. It is also an independent predictor for poor prognosis and may be a useful biomarker for targeted therapy and prognostic evaluation.

Identification of epigenetic silencing of GCNT2 expression by comprehensive real-time PCR screening in colorectal cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 506-506
Author(s):  
Kazunorii Nakamura ◽  
Horomichi Sawaki ◽  
Keishi Yamashita ◽  
Masahiko Watanabe ◽  
Hisashi Narimatsu
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Real Time ◽  
Cell Lines ◽  
Real Time Pcr ◽  
Critical Role ◽  
Normal Mucosa ◽  
Primary Cancer ◽  
Normal Tissues ◽  
Cancer Tissues

506 Background: Glycoprotein expression profile has been proved to be dramatically altered in human cancers, however specific glycogenes which are aberrant in expression in cancer cells has not been fully identified. Recent accumulated evidence supported notion that the reduced expression of tumor suppressor genes is explained by DNA promoter methylation in human cancer. Methods: We used Comprehensive Real time PCR system (CRPS) for glycogenes (189 genes) to identify genes aberrantly expressed in colorectal cancer tissues (CRC) as compared to the corresponding normal mucosa tissues. GCNT2 was of particular interest among the identified genes in CRC. Results: (1) GCNT2 harbors 3 isoforms which have different promoter regions. (2) All of the 3 isoforms of GCNT2 genes were remarkably decreased in CRC as compared to the corresponding normal mucosa, and each isoform expression was strongly associated with other 2 isoforms in primary cancer tissues by TaqMan real time PCR (R = 0.99-995, p < 0.0001). (3) Among the 5 CRC cell lines (DLD1, HCT116, CACO2, LOVO), those which were silenced in expression were reactivated by demethylating agents such as 5-aza-2’ deoxycytidine and trichostatin A. (4) Promoter region of the variant 2 of GCNT2 was consistent with its silenced expression in CRC cell lines by cloned sequence, so we examined DNA methylation status of the promoter of the GCNT2 variant 2 in 50 primary cancer tissues and the corresponding normal tissues. Quantitative MSP revealed that almost half of normal tissues have methylation as high as tumor tissues, while, in the primary CRC with less methylation in the corresponding normal tissues, DNA methylation was higher in primary CRC tissues than in the corresponding normal tissues. Finally, GCNT2 variant 2 stable transfection induced expression of other 2 isoform variants. Conclusions: We identified novel methylation gene GCNT2 among the glycoenes. Glycoenes that were altered in genomic or epigenetic manner have been few, so GCNT2 may play a critical role in cancer progression through glycan change.

Effect of thymidine kinase 1 expression on prognosis and treatment outcomes in refractory metastatic colorectal cancer: Results from two randomized studies of TAS-102 versus a placebo.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 529-529 ◽  
Author(s):  
Takayuki Yoshino ◽  
Eiji Shinozaki ◽  
Kentaro Yamazaki ◽  
Yoshito Komatsu ◽  
Tomohiro Nishina ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Treatment Outcomes ◽  
Thymidine Kinase ◽  
Antitumor Agent ◽  
Thymidine Kinase 1 ◽  
Poor Prognostic Factor ◽  
Intention To Treat ◽  
Baseline Characteristics ◽  
Occupancy Rates

529 Background: TAS-102 is an oral nucleoside antitumor agent, comprising trifluridine (FTD) and tipiracil. FTD is incorporated into DNA after phosphorylation by thymidine kinase 1 (TK1). This study aimed to investigate the association between TK1 expression and TAS-102 efficacy in refractory metastatic colorectal cancer (mCRC) patients (pts). Methods: Data from two randomized phase 2 and phase 3 studies of mCRC pts refractory to standard therapies were analyzed for treatment outcomes in relation to TK1 expression. Expression was measured using immunohistochemistry, and staining was classified according to intensity and scored 0, 1+, 2+, or 3+. Occupancy rates of the areas scored 2+ and 3+ in tumor cells were calculated in 5% intervals, and divided into two groups (high or low TK1) at each cut-off point. Results: TK1 expression was evaluated in 329 pts. Baseline characteristics and treatment outcomes were comparable between the TK1-refined and intention-to-treat populations. Pts with high TK1 expression who received the placebo had a poor prognosis, while those receiving TAS-102 showed a significant improvement in overall survival (OS) at cut-off points of 5% to 15%, and 30%. Conclusions: High TK1 expression could be a poor prognostic factor and a predictive factor of TAS-102 efficacy in mCRC pts. [Table: see text]

Mutation analysis in the coding sequence of thymidine kinase 1 in breast and colorectal cancer

2003 ◽  
Vol 18 (1) ◽  
pp. 1-6 ◽  
Author(s):  
S.I. Gilles ◽  
S. Romain ◽  
P. Casellas ◽  
L.H. Ouafik ◽  
F. Fina ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Thymidine Kinase ◽  
Mutation Analysis ◽  
Thymidine Kinase 1 ◽  
Coding Sequence

The Regional Specificity of Mucosa-Associated Microbiota in Patients with Distal Colorectal Cancer

Digestion ◽  
2021 ◽  
pp. 1-9
Author(s):  
Yoshihiko Kono ◽  
Ryo Inoue ◽  
Takumi Teratani ◽  
Mineyuki Tojo ◽  
Yuko Kumagai ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Fusobacterium Nucleatum ◽  
Amplicon Sequencing ◽  
Normal Mucosa ◽  
Rrna Gene ◽  
Normal Tissues ◽  
Streptococcus Anginosus ◽  
Significant Difference ◽  
Regional Specificity ◽  
Tissue Specimens

<b><i>Background/Aims:</i></b> Recent studies have demonstrated that the populations of several microbes are significantly increased in fecal samples from patients with colorectal cancer (CRC), suggesting their involvement in the development of CRC. The aim of this study was to identify microbes which are increased in distal CRCs and to identify the specific location of microbes increased in mucosal tissue around the tumor. <b><i>Methods:</i></b> Tissue specimens were collected from surgical resections of 28 distal CRCs. Five samples were collected from each specimen (location A: tumor, B: adjacent normal mucosa, C: normal mucosa 1 cm proximal to the tumor, D: normal mucosa 3 cm proximally, and E: normal mucosa 6 cm proximally). The microbiota in the sample were analyzed using 16S rRNA gene amplicon sequencing and the relative abundance (RA) of microbiota compared among the 5 locations. <b><i>Results:</i></b> At the genus level, the RA of <i>Fusobacterium</i> and <i>Streptococcus</i> at location A was the highest among the 5 locations, significantly different from that in location E. The dominant species of each genus was <i>Fusobacterium nucleatum</i> and <i>Streptococcus anginosus.</i> The RAs of these species gradually decreased from locations B to E with a statistically significant difference in <i>F. nucleatum</i>. The genus <i>Peptostreptococcus</i> also showed a similar trend, and the RA of <i>Peptostreptococcus stomatis</i> in location A was significantly associated with depth of tumor invasion and tumor size. <b><i>Conclusion:</i></b> Although the clinical relevance is not clear yet, these results suggest that <i>F. nucleatum, S. anginosus</i>, and <i>P. stomatis</i> can spread to the adjacent normal tissues and may change the surrounding microenvironment to support the progression of CRC.

Methylenetetrahydrofolate Reductase C677T is Not Associated with Expression of Pyrimidine Metabolic Enzyme Genes in Colorectal Cancer

2006 ◽  
Vol 34 (3) ◽  
pp. 307-315 ◽  
Author(s):  
R Takeda ◽  
T Kamano ◽  
K Sakamoto ◽  
M Sugano ◽  
S Hosoda ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Methylenetetrahydrofolate Reductase ◽  
Dihydropyrimidine Dehydrogenase ◽  
Mrna Level ◽  
Mthfr C677t ◽  
Normal Mucosa ◽  
Metabolic Enzyme ◽  
C677t Polymorphism ◽  
Mthfr C677t Polymorphism ◽  
Normal Tissues

Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism may influence the chemosensitivity of colorectal cancers to fluorouracil (5-FU) by increasing intracellular 5, 10-methylenetetrahydrofolate. The effect of this polymorphism on the expression of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyl transferase (OPRT) and thymidine phosphorylase (TP) in colorectal cancer was investigated. The MTHFR C677T polymorphism was analysed and TS, DPD, OPRT and TP mRNA expression was measured in tumour and adjacent normal mucosal tissue. In all patients, the genotypes of the tumour and normal tissues were identical. No differences were found in the expression of TS, DPD or TP mRNA by genotype in either tumour or normal tissue. Although the OPRT mRNA level in tumour tissue was not associated with the genotype, normal mucosa with the TT genotype showed a significantly higher OPRT mRNA level than mucosa with other genotypes. The MTHFR C667T polymorphism is not associated with intratumoural expression of TS, DPD, OPRT or TP.

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