Role of ERCC1, XRCC3, Aurora A and TGFBR1 single-nucleotide polymorphisms (SNP) and CHFR and 14–3-3σ methylation in a customized cisplatin (cis) trial based on ERCC1 mRNA levels in stage IV non-small cell lung cancer (NSCLC) patients (pts)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7687-7687
Author(s):  
M. Taron ◽  
M. Cobo ◽  
D. Isla ◽  
B. Massuti ◽  
A. Montes ◽  
...  
Keyword(s):  
Performance Status ◽  
Stage Iv ◽  
Taqman Assay ◽  
Lower Probability ◽  
Mrna Levels ◽  
Nucleotide Polymorphisms ◽  
Aurora A ◽  
Specific Pcr ◽  
Best Response

7687 Background: The primary aim of this trial was response. In both the control arm and in the genotypic arm with low tumor ERCC1 mRNA levels, pts received docetaxel (doc)/cis; in the genotypic arm with high tumor ERCC1 mRNA levels, pts received doc/gemcitabine. Response was significantly higher in the genotypic arms. We examined 324 pts for genetic markers that could influence response, including ERCC1 118 C/T, ERCC1 C8092A, XRCC3 241 (Thr to Met), Aurora A 91 T>A, Aurora A 169G>A, a SNP within intron 7 of the TGFBR1 gene (Int7G24A), and an in-frame germline deletion (TGFBR1*6A). Methylation of 14–3-3s and CHFR were also analyzed. Methods: DNA from peripheral lymphocytes was used for genotyping (Taqman assay) and methylation-specific PCR was used for 14–3- 3s and CHFR in pretreatment serum DNA. Results: There were no differences in clinical characteristics among the different SNP types, except that pts with Aurora A 91 AA had higher tumor ERCC1 mRNA levels (P=0.005). No relationship was found between ERCC1 SNPs and tumor ERCC1 mRNA levels. A strong correlation was found between the Int7G24A and XRCC3 241 SNPs (P=0.03). The Int7G24A GA type had a higher odds ratio (OR) of response (OR 2.32) than the AA type (OR 3.15) (P=0.02). XRCC3 241 MetMet had a lower probability of response (OR 0.23) (P=0.04). No other differences in response were observed according to any of the other SNPs or methylation. In the multivariate model, the best response was observed in pts with performance status (PS) 0, low ERCC1 levels, and XRCC3 241 SNP ( Table ). Conclusions: Further research is warranted to define the role of theTGFBR1 Int7G24A gene in customized treatments. No significant financial relationships to disclose. [Table: see text]

Excision cross-complementing group 1 (ERCC1) single nucleotide polymorphisms (SNPs) and survival in cisplatin (cis)/docetaxel (doc)-treated stage IV non-small cell lung cancer (NSCLC) patients (p): A Spanish Lung Cancer Group study

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7053-7053 ◽  
Author(s):  
M. Taron ◽  
V. Alberola ◽  
G. Lopez Vivanco ◽  
C. Camps ◽  
R. De Las Peñas ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Excision Repair ◽  
Performance Status ◽  
Stage Iv ◽  
Dna Lesions ◽  
Taqman Assay ◽  
Nucleotide Polymorphisms ◽  
Cancer Group ◽  
Nucleotide Excision Repair Pathway ◽  
Nsclc Patients

7053 Background: SNPs are the result of historical errors in DNA replication or repair that have been inherited through generations and are now shared among individuals. ERCC1 belongs to the nucleotide excision repair pathway. We examined whether ERCC1 SNPs 118 C/T and C8092A affect the repair of cis DNA lesions and thereby influence survival in cis-treated NSCLC p. Methods: SNP genotyping of ERCC1 118C/T and C8092A was performed by the TaqMan assay, and results were correlated with median survival (MS) in 706 cis/doc-treated stage IV NSCLC p. Results: Characteristics: 590 male, 116 female; performance status (PS) 0: 216 p (30.6%), PS 1: 480 p (68%), PS 2: 10 p (1.4%); adenocarcinoma, 371 p (53%). Overall response rate: 30%. After a median follow-up of 7.8 months (m) (range, 1–47 m), overall MS was 8.9 m. SNP frequencies: 118 T/T, 40.2%; C/T, 45.4%; C/C, 14.4%; C8092A C/C, 57.6%; C/A, 36%; A/A, 6.4%. MS according to 118 C/T SNP: T/T, 8.9 m; C/T, 9.5 m; C/C, 10 m (P = 0.51). MS according to C8092A SNP: C/C, 9.3 m; C/A, 10.2 m; A/A, 7.2 m (P = 0.05). When stratified by PS, the association between C8092A and MS is stronger for p with PS 0: C/C, 15.9 m; C/A, 13.8 m; A/A, 8.7 m (P = 0.04). Conclusions: This is the largest study to date reporting the effect of ERCC1 C8092A SNP on MS in stage IV NSCLC p treated with a single regimen. The uncommon A/A genotype predicts poor survival in p treated with dis/doc. No significant financial relationships to disclose.

Mitotic checkpoint gene CHFR methylation in pretreatment serum DNA of docetaxel (doc)/cisplatin (cis)-treated stage IV non-small cell lung cancer (NSCLC) patients (p)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7056-7056 ◽  
Author(s):  
D. Isla ◽  
F. Salazar ◽  
J. Ramirez ◽  
M. Sanchez Ronco ◽  
M. Cobo ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Performance Status ◽  
Ring Finger ◽  
Stage Iv ◽  
Mitotic Checkpoint ◽  
Mrna Levels ◽  
Specific Pcr ◽  
Enhanced Sensitivity ◽  
Frequent Event ◽  
Serum Dna

7056 Background: CHFR (checkpoint with forkhead-associated and ring finger) regulates a prophase delay in cells exposed to agents that disrupt microtubules. Epigenetic inactivation of CHFR is a frequent event in human tumors, leading to impaired checkpoint function and enhanced sensitivity to docetaxel. We hypothesized that serum DNA methylation of CHFR could be a predictor of longer survival in p treated with doc/cis. Methods: Sodium bisulfite modified serum DNAwas used as the template for methylation-specific PCR assay. DNA was obtained from 600 doc/cis-treated stage IV NSCLC p. Results: Preliminary data on 301 p is available. The frequency of CHFR hypermethylation was 32.6%. There was no association between methylation and performance status (PS), age, gender, histology, response, 14–3-3σ serum DNA methylation, polymorphisms in lymphocyte DNA (ERCC1 118 C/T, ERCC1 C8092A, XRCC3 241 ThrMet), or tumor ERCC1 mRNA levels. Overall, there was a tendency to better median survival (MS) for p with methylated CHFR. In p with PS 0, MS was 33 months (m) for 41 p with methylated CHFR and 12 m for 64 p with unmethylated CHFR (P = 0.23). In p >66 years (y), MS was not reached for 31 p with methylated CHFR and 9.6 m for 80 p with unmethylated CHFR (P = 0.01), while in p <66 y, MS was 9.4 m for 67 p with methylated CHFR and 10 m for 123 p with unmethylated CHFR (P = 0.62). p with both 14–3-3σ and CHFR methylation showed a tendency to longer survival. Final data on 600 p will be presented. Conclusions: Early findings indicate that CHFR methylation in elderly p predicts a significant survival benefit in doc/cis-treated NSCLC. No significant financial relationships to disclose.

scholarly journals Microsatellite Instability and MMR Genes Abnormalities in Canine Mammary Gland Tumors

Diagnostics ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 104 ◽  
Author(s):  
Faiz Muhammad Khand ◽  
Da-Wei Yao ◽  
Pan Hao ◽  
Xin-Qi Wu ◽  
Asghar Ali Kamboh ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Microsatellite Instability ◽  
The Other ◽  
Control Group ◽  
Mrna Levels ◽  
Nucleotide Polymorphisms ◽  
Mmr Genes ◽  
Mammary Gland Tumors ◽  
Canine Mammary Gland

Early diagnosis of mammary gland tumors is a challenging task in animals, especially in unspayed dogs. Hence, this study investigated the role of microsatellite instability (MSI), MMR gene mRNA transcript levels and SNPs of MMR genes in canine mammary gland tumors (CMT). A total of 77 microsatellite (MS) markers in 23 primary CMT were selected from four breeds of dogs. The results revealed that 11 out of 77 MS markers were unstable and showed MSI in all the tumors (at least at one locus), while the other markers were stable. Compared to the other markers, the ABC9TETRA, MEPIA, 9A5, SCNA11 and FJL25 markers showed higher frequencies of instability. All CMT demonstrated MSI, with eight tumors presenting MSI-H. The RT-qPCR results revealed significant upregulation of the mRNA levels of cMSH3, cMLH1, and cPMSI, but downregulation of cMSH2 compared to the levels in the control group. Moreover, single nucleotide polymorphisms (SNPs) were observed in the cMSH2 gene in four exons, i.e., 2, 6, 15, and 16. In conclusion, MSI, overexpression of MMR genes and SNPs in the MMR gene are associated with CMT and could be served as diagnostic biomarkers for CMT in the future.

High correspondence between EGFR mutations in tissue and in circulating DNA form non-small-cell lung cancer (NSCLC) patients (p) with poor performance status (PS)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7505-7505 ◽  
Author(s):  
T. Moran ◽  
L. Paz-Ares ◽  
D. Isla ◽  
M. Cobo ◽  
B. Massuti ◽  
...  
Keyword(s):  
Tumor Tissue ◽  
Performance Status ◽  
Stage Iv ◽  
Poor Performance ◽  
Egfr Mutations ◽  
Taqman Assay ◽  
Poor Performance Status ◽  
Nsclc Tissue ◽  
Exon 19 Deletion ◽  
Exon 19

7505 Background: We evaluated the correspondence between EGFR mutations in NSCLC tissue and matched serum DNA and the value of EGFR mutations as a serological marker. Methods: 121 Spanish stage IV NSCLC p received customized first- or second-line erlotinib monotherapy based on the presence of EGFR mutations in the tumor tissue. Serum genomic DNA was obtained from all p prior to erlotinib administration. EGFR exon 19 deletions were studied by length analysis of fluorescently labeled PCR products and the exon 21 L858R mutation by a PCR Taqman assay. Results: The EGFR mutation status in the serum was consistent with that in the tumor tissue of 82/121 p (68%) and of 15/16 p (93.8%) with PS 2 had mutations. Overall, 64.3% of p had an exon 19 deletion and 35.7% had L858R. 78% of mutations were found in females (P=0.01) and 77.6% in never-smokers (P=0.07). Response rate was 88% in p with mutations only in the tumor and 87% in p with mutations in tumor and serum. Complete responses were observed in 20% of p with mutations in tumor and serum vs 4% of p with mutations only in tumor (P=0.09). With a median follow-up of 6.8 months (m) (range, 1.2–17.6), time to progression (TTP) and median survival have not been reached. A trend to better outcome was seen in p without serum EGFR mutations. TTP was longer for p with EGFR exon 19 deletions (not reached) than for p with L858R (7.7 m) (P=0.02). TTP for p with PS 2 with exon 19 deletions was not reached, while it was 2.7 m for p with L858R (P=0.17). Conclusions: EGFR mutations in serum could be a non-invasive source of information on the genotype of the original tumor cells and could be a useful tool to predict p response to erlotinib, especially in p with poor PS. No significant financial relationships to disclose.

Observing patients with advanced non-small cell lung cancer (NSCLC): An overview of real world treatments and outcomes in Europe

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7626-7626
Author(s):  
H. G. Bischoff ◽  
H. Anderson ◽  
B. van den Borne ◽  
F. Langer ◽  
M. I. Leschinger ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Observational Study ◽  
Large Scale ◽  
Advanced Nsclc ◽  
Performance Status ◽  
Stage Iv ◽  
Complete Response ◽  
First Line ◽  
Best Response ◽  
Clinical Trial Results

7626 Background: ACTION (Assessment of Costs and ouTcomes of chemotherapy In an Observational setting in patients with advanced NSCLC) is a prospective, pan-European observational study. The objective of ACTION is to describe advanced NSCLC treatment in routine clinical practice. Methods: Chemonaive patients (pts) aged = 18 yrs with stage IIIb/IV NSCLC were observed for 18 months from presentation for initiation of chemotherapy (CT). All pt care, including CT given, was at the discretion of the pt/physician. Pts were excluded if participating in a clinical trial. Results: 975 pts [Germany (571), UK (193), Finland (99), Netherlands (76), Portugal (36)] were enrolled from April 2003 to September 2004 and observations completed June 2006. Median age was 65 yrs (32–90) with 28.3% of pts aged =70 yrs; 71.3% were male; 65.2% had stage IV disease. WHO performance status (PS) was 0/1 (86.2%), 2 (10.0%), 3/4 (3.8%). Of 487 pts who experienced weight loss, 172 (33.4%) lost >10% body weight in 4 weeks prior to start of CT. First-line CT given: gemcitabine (gem) 10.3%, vinorelbine (vin) 4.3%, gem+platinum 45.0%, vin+platinum 14.6%, taxane+platinum 11.7%, other 14.2%. Complete response (CR) to first-line CT was observed in 1.8% of pts, partial response (PR) 37.9%, stable disease (SD) 28.5%, progressive disease (PD) 17.8%, unknown 13.8%. Second-line CT was planned for 29.2% (285) pts. Median time from initiation of 1st-line to initiation of 2nd-line CT was 5.8 months. Median age was 62 yrs (32–84); 69.8% were male; WHO PS at initiation of 2nd line CT: 0/1 (79%), 2 (17%), 3/4 (4%). Best response to 2nd-line CT: CR 0.4%, PR 9.1%, SD 19.3%, PD 48.8%, unknown 14.3%. Unadjusted median survival time for all pts: 9.3 months (95% CI 8.6–10.3). Overall estimated 1-yr survival was 39.5%. Conclusions: ACTION was the first large-scale observational study in pts with advanced NSCLC in Europe. Overall response rates and survival were consistent with clinical trial results, even though approximately one- third of pts enrolled may have been excluded from clinical trials on the basis of their baseline demographics. No significant financial relationships to disclose.

scholarly journals Methylation and Gene Expression of BCAT1 and IKZF1 in Colorectal Cancer Tissues

2018 ◽  
Vol 12 ◽  
pp. 117955491877506 ◽  
Author(s):  
Maher Jedi ◽  
Graeme P Young ◽  
Susanne K Pedersen ◽  
Erin L Symonds
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Messenger Rna ◽  
Stage Iv ◽  
Mrna Levels ◽  
Polymerase Chain ◽  
Cancer Tissues ◽  
The Relationship ◽  
Neoplastic Tissues

The genes BCAT1 and IKZF1 are hypermethylated in colorectal cancer (CRC), but little is known about how this relates to gene expression. This study assessed the relationship between methylation and gene expression of BCAT1 and IKZF1 in CRC and adjacent non-neoplastic tissues. The tissues were obtained at surgery from 36 patients diagnosed with different stages of CRC (stage I n = 8, stage II n = 13, stage III n = 10, stage IV n = 5). Methylated BCAT1 and IKZF1 were detected in 92% and 72% CRC tissues, respectively, with levels independent of stage ( P > .05). In contrast, only 31% and 3% of non-neoplastic tissues were methylated for BCAT1 and IKZF1, respectively ( P < .001). The IKZF1 messenger RNA (mRNA) expression was significantly lower in the cancer tissues compared with that of non-neoplastic tissues, whereas the BCAT1 mRNA levels were similar. The latter may be due to the BCAT1 polymerase chain reaction assay detecting more than 1 mRNA transcript. Further studies are warranted to establish the role of the epigenetic silencing of IKZF1 in colorectal oncogenesis.

scholarly journals Role of Human Papillomavirus and Its Association With an Indian OSCC Subjects

2021 ◽  
Author(s):  
Amisha Patel ◽  
Vijaykumar Gupta ◽  
Sejal Shah
Keyword(s):  
Oral Cancer ◽  
Stage Iv ◽  
Hpv Infection ◽  
Infection Frequency ◽  
Papilloma Virus ◽  
Exact Test ◽  
Specific Pcr ◽  
Tobacco Addiction ◽  
Pcr Method

Abstract Oral Cancer; especially Oral Squamous Cell Carcinoma (OSCC) is the eighth most common cancer all over the globe and most common neoplasm in India. Due to the tobacco addiction pattern in Indians specially Guajarati’s are well known for high consumption of tobacco in non-smoking form may have the high-risk for developing oral cancer. Apart of this, Human papilloma virus(HPV) might be one of the cause for developing oral cancer hence, the proposed study was carried out for 50 primary OSCC subjects from January 2018 to October 2018. Tumour specimens were HPV-genotyped by type specific PCR method. Statistical analyses were performed by Fisher’s exact test. The present study identified 4% HPV infection frequency in advanced staged OSCC Indian subset, where One OSCC stage IV patient observed with HPV 16 infection and one OSCC stage III patient with HPV 18. Our finding differs with rest of the population, as the region have high amount of consumption of tobacco. Current study need to be validated in larger sample size to get the clear view for association of HPV with oral cancer.

Excision repair cross complementing 6 (ERCC6) single nucleotide polymorphism (SNP) and outcome to gemcitabine (gem)/cisplatin (cis) or docetaxel (doc)/cis in stage IV non-small cell lung cancer (NSCLC) patients (pts)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7605-7605
Author(s):  
O. Etxaniz ◽  
M. Provencio ◽  
J. Terrasa ◽  
A. Carrato ◽  
P. Lianes ◽  
...  
Keyword(s):  
Chemotherapy Regimen ◽  
Excision Repair ◽  
Performance Status ◽  
Stage Iv ◽  
Gender Performance ◽  
Differential Sensitivity ◽  
Taqman Assay ◽  
Base Excision ◽  
Nsclc Patients ◽  
Base Excision Dna Repair

7605 Background: ERCC6 (alternate name CSB) is involved in both transcription coupled and base excision DNA repair, and the ERCC6 C-6530>G SNP is involved in gene regulation. Different levels of ERCC6 mRNA expression have been observed in cells according to ERCC6–6530 genotype. Methods: We investigated the ERCC6 C-6530>G SNP in 309 stage IV NSCLC pts treated with doc/cis (196 pts) and gem/cis (113 pts). DNA was extracted from peripheral lymphocytes and Taqman assay was used for SNP typing. Results: Distribution of ERCC6 genotypes was: CC 113 pts (36.6%); CG 157 pts (50.8%); GG 39 pts (12.6%). No differences in genotype were observed according to age, gender, performance status (PS), histology, chemotherapy regimen or second-line treatment. Overall time to progression (TTP) was 5.4 months (m) and median survival (MS) 9.9 m. No differences in TTP or MS were observed according to ERCC6 SNP types. However, when pts were broken down by chemotherapy regimen, TTP was 7 m for 31 CC pts treated with gem/cis and 5.4 m for 71 CC pts treated with doc/cis (P=0.04) ( Table ). MS was longer for CC pts treated with gem/cis (11 m) than for CC pts treated with doc/cis (8.9 m) (P=0.46). Differences were also observed in pts with PS 0 and in younger pts. Conclusions: ERCC6 C-6530>G SNP may confer differential sensitivity to gem or doc in combination with cis. We hypothesize that ERCC6 6350 CC is a surrogate of ERCC6 transcript, where lower ERCC6 expression levels may increase the activity of gem/cis in comparison to doc/cis. No significant financial relationships to disclose. [Table: see text]

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