scholarly journals POFUT1 as a Promising Novel Biomarker of Colorectal Cancer

Cancers ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 411 ◽  
Author(s):  
Julien Chabanais ◽  
François Labrousse ◽  
Alain Chaunavel ◽  
Agnès Germot ◽  
Abderrahman Maftah
Keyword(s):  
Colorectal Cancer ◽  
Mucinous Adenocarcinoma ◽  
Copy Number ◽  
Notch Pathway ◽  
Gene Copy Number ◽  
Stage I ◽  
Gene Copy ◽  
Pathway Activation ◽  
Potential Biomarker ◽  
Cancer Types

Background: While protein O-fucosyltransferase 1 (POFUT1) overexpression has been recently proposed as a potential biomarker for different cancer types, no study was carried out on POFUT1 implication in colorectal cancer (CRC). Methods: Data from 626 tumors and 51 non-tumor adjacent tissues available in FireBrowse had been used in this study. Statistical analyses on POFUT1 expression and gene copy number, NOTCH receptors (main targets of POFUT1 enzymatic activity) expression and association of POFUT1 and NOTCH1 expressions with clinical parameters were investigated. Data were completed by POFUT1 histological labeling on six tumor tissues from patients with CRC. Results: We found that POFUT1 is overexpressed from the stage I (p < 0.001) and 76.02% of tumors have a 20q11.21 amplification, associated in 90.13% of cases with a POFUT1 overexpression, compared to non-tumor adjacent tissues. The POFUT1 copy number in tumors is mainly between 2 and 3. POFUT1 is positively correlated with NOTCH1 (rs = 0.34, p < 0.001), NOTCH3 (rs = 0.087, p = 0.0297), and NOTCH4 (rs = 0.097, p = 0.0148) expressions, while negatively correlated with NOTCH2 expression (rs = −0.098, p = 0.0142). POFUT1 overexpression is markedly associated with rectal location, non-mucinous adenocarcinoma and cancer stages IV and M1. NOTCH1 overexpression is only associated with rectal location and non-mucinous adenocarcinoma. Conclusion: We conclude that POFUT1 is overexpressed in CRC from stage I, and its high expression is associated with metastatic process, probably through NOTCH pathway activation. Then, POFUT1 could represent a potential novel biomarker for CRC diagnosis.

scholarly journals Topoisomerase 1(TOP1 ) gene copy number in stage III colorectal cancer patients and its relation to prognosis

2012 ◽  
Vol 7 (1) ◽  
pp. 101-111 ◽  
Author(s):  
Maria Unni Rømer ◽  
Sune Boris Nygård ◽  
Ib Jarle Christensen ◽  
Signe Lykke Nielsen ◽  
Kirsten Vang Nielsen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Copy Number ◽  
Gene Copy Number ◽  
Stage Iii ◽  
Gene Copy ◽  
Topoisomerase 1 ◽  
Colorectal Cancer Patients

scholarly journals hTERT gene copy number is not associated with hTERT RNA expression or telomerase activity in colorectal cancer

2005 ◽  
Vol 116 (3) ◽  
pp. 395-400 ◽  
Author(s):  
Richard Palmqvist ◽  
Anju Zhang ◽  
Dawei Xu ◽  
Irina Golovleva ◽  
Karl-Fredrik Norrback ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Copy Number ◽  
Gene Copy Number ◽  
Telomerase Activity ◽  
Gene Copy ◽  
Rna Expression ◽  
Htert Gene

Epidermal growth factor gene amplification is not frequent and cannot account for antitumor activity of cetuximab plus chemotherapy in advanced colorectal cancer patients

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3561-3561 ◽  
Author(s):  
C. Garufi ◽  
M. Mottolese ◽  
A. Cianciulli ◽  
M. Zeuli ◽  
S. Buglioni ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Antitumor Activity ◽  
Cancer Patients ◽  
Copy Number ◽  
Advanced Colorectal Cancer ◽  
Gene Copy Number ◽  
Chromosome 7 ◽  
Gene Copy ◽  
Egfr Gene ◽  
Colorectal Cancer Patients

3561 Cetuximab has been shown to be active in the metastatic colorectal cancer, but EGFR detection by immunohistochemistry is not predictive for tumor response. Moroni et al (Lancet Oncology 2005) showed that, in patients responsive to Cetuximab, EGFR gene copy number, assessed by FISH, was increased. On this basis, copy number and protein status of EGFR were investigated in 70 primary and/or metastatic colorectal carcinomas. Protein expression was assessed by immunohistochemistry (IHC) using DAKO EGFRPharmDX kit. Gene and chromosome 7 copy numbers were identified by fluorescent in situ hybridization (FISH). Dual-target, dual-color FISH assays were performed using the LSI EGFR SpectrumOrange/CEP 7 Spectrum Green probe. EGFR gene copy number, chromosome 7 copy number and the average EGFR gene to chromosome 7 signal ratio were reported as FISH genetic variables. Chromosome 7 was polysomic when cancer cells showed multiple centromere signals: low polysomy (2 to 5 signals), high polysomy (>5 signals). Samples with a ratio value ≥ 2.0 were considered to be amplified. EGFR protein was overexpressed in 57 out of 70 patients (81%). In the group of 58 patients evaluated as polysomic, 48 (82,7%) had a low polysomy level, whereas 20 (12.7%) had a high polysomy level. Gene amplification was seen only in 3/70 patients. High polysomy was evidenced only in the group of patients displaying an EGFR IHC score 2+/3+. Forty-six pretreated patients received a cetuximab-based treatment. Response to treatment has been already evaluated in 26 FISH-negative patients while for the other 20 it is still too early. We observed 7 PR (27%), 9 SD (35%) and 10 PD (38%). This study shows that in this series of advanced colorectal cancer patients, EGFR amplification, measured by FISH, is a rare event (4%) and could be considered together with chromosome 7 polysomy for the antitumor activity. No significant financial relationships to disclose.

Increased gene copy number and amplification of FGF2 and FGFR1 in metastatic colorectal cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 402-402 ◽  
Author(s):  
Christopher Hanyoung Lieu ◽  
Marileila Varella-Garcia ◽  
Liang Guo Xu ◽  
Zhi-Qin Jiang ◽  
S. Gail Eckhardt ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Metastatic Colorectal Cancer ◽  
Copy Number ◽  
Resistance Mechanism ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Cell Range ◽  
Previously Treated ◽  
Fgfr1 Gene

402 Background: Fibroblast growth factors (FGFs) and their receptors (FGFRs) play essential roles in tightly regulating cell proliferation, survival, migration, and angiogenesis in cancers. However, gene copy number and amplification of FGF2 and FGFR1 have not been extensively evaluated in patients with metastatic colorectal cancer (CRC). Methods: Two tissue microarrays (TMA) were constructed with resected CRC liver metastases from 120 patients. The TMAs included duplicated intratumoral regions and the invasive margin between tumor and normal hepatic parenchyma. Patients were either untreated, or previously treated with FOLFIRI or FOLFOX +/- bevacizumab. The TMA slides were subjected to a two-color FISH assay using a mixture of FGF2 and FGFR1 in-house developed probes. Results: Results were obtained from 118 patients. The analysis detected an average of 1.90 copies of FGF2 signal per cell (range, 1.10-3.46 copies) and an average of 2.27 copies of FGFR1 signal per cell (range, 1-12-7.14 copies). Three control specimens from each slide were also scored, with an average of 1.74 copies of FGF2 and 1.73 copies of FGFR1. High copy number per cell (mean > 2.5 copies) was detected in 9.3% of specimens for FGF2 and 27.9% for FGFR1, including 2 patients (1.7%) for FGF2 and 5 (4.2%) for FGFR1 with focal amplification, defined by ≥ 10% cells with > 4 copies. Additionally, duplications of gene signals in the same locus were detected in 10 samples (8.5%) for FGF2 and 19 (16.1%) for FGFR1. Intratumoral heterogeneity was rare (detected in 3 patients). There was no statistically significant correlation between FGF2 or FGFR1 gene copy number and prior treatment, pathologic response, relapse free survival, or overall survival, though there was a trend towards higher FGFR1 gene copy number in patients previously receiving bevacizumab (p=0.07). Conclusions: Both FGF2 and FGFR1 display variable copy number among resected CRC liver metastases, with larger variability detected for FGFR1. Gene amplification was rare but detected in several patients for both FGF2 and FGFR1. Follow up studies will investigate higher FGFR1 gene copy number in patients previously treated with bevacizumab, perhaps reflecting a potential escape or resistance mechanism.

Assessment of the topoisomerase I gene copy number as a predictive biomarker of objective response to irinotecan in metastatic colorectal cancer

2013 ◽  
Vol 49 (1) ◽  
pp. 84-91 ◽  
Author(s):  
Sune Boris Nygård ◽  
Ib Jarle Christensen ◽  
Signe Lykke Nielsen ◽  
Hans Jørgen Nielsen ◽  
Nils Brünner ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Copy Number ◽  
Topoisomerase I ◽  
Objective Response ◽  
Gene Copy Number ◽  
Predictive Biomarker ◽  
Gene Copy ◽  
I Gene

KRAS mutation is highly predictive of cetuximab resistance in metastatic colorectal cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10502-10502 ◽  
Author(s):  
F. Di Fiore ◽  
F. Le Pessot ◽  
A. Lamy ◽  
F. Charbonnier ◽  
J. Sabourin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Predictive Factors ◽  
Kras Mutation ◽  
Copy Number ◽  
Gene Copy Number ◽  
Gene Mutations ◽  
Gene Copy ◽  
Kras Gene ◽  
Egfr Gene

10502 Background: In metastatic colorectal cancer (MCRC), no molecular predictive markers to cetuximab response have been yet established. The aim was to evaluate whether KRAS gene mutations, EGFR immunochemistery (IHC) and EGFR gene copy number correlate with response to cetuximab. Methods: 59 patients with MCRC treated by cetuximab between July 2004 and December 2005 were retrospectively included. Clinical data were collected and tumour response was evaluated according to RECIST criteria. EGFR IHC was performed using the Dako kit. The EGFR gene copy number was determined by FISH (Fluorescence in-Situ Hybridization). Detection of KRAS gene mutations on exon 2 was performed by sequencing of extracted paraffin-embedded DNA and then by 2 methods, SNaPshot and PCR-LCR, specifically developed to detect small fractions of mutated tumor cells. Response to cetuximab was studied according to clinical data, IHC, FISH and KRAS mutation analysis using the Fischer exact test. Predictive factors of response were determined by logistic regression. Skin reactions were collected but not considered for this analysis as regards the lack of accurate grading in a retrospective study. Times to progression (TTP) were calculated using the Kaplan-Meier method and compared with log-rank test. Results: 12 patients (20.3%) responded to cetuximab (2 patients with complete response and 10 patients with partial response), 19 (32.2%) had stable disease and 28 (47.5%) were in disease progression. A KRAS mutation was detected in 22/59 tumours and, in 6 cases, was missed by sequencing analysis but detected using the SNaPshot and PCR-LCR assays. No KRAS mutation was found in responders patients. KRAS mutation was associated with disease progression (p = 0.0005) and TTP was significantly decreased in mutated KRAS patients (3 vs 5.5 months, p = 0.015). There was no correlation between EGFR IHC and cetuximab response. No EGFR gene copy number increase was detected in responders patients. Predictive factors of cetuximab resistance were KRAS mutation (p=0.003; OR:0.10; 95IC:0.22–0.40) and age<60 (p=0.024; OR:0.13; 95IC:0.02–0.77). Conclusions: KRAS mutation is highly predictive of cetuximab resistance in MCRC. Our study also highlights the need of sensitive methods to ensure an efficient mutation detection. No significant financial relationships to disclose.

EGFR gene copy number to predict response to anti-EGFR treatment and survival in RAS wild type and RAS/BRAF/PIK3CA wild type metastatic colorectal cancer.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. e15108-e15108
Author(s):  
Olli Carpen ◽  
Annika Ålgars ◽  
Jari Sundström ◽  
Soili Kytölä ◽  
Pia Österlund ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Copy Number ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Wild Type ◽  
Egfr Gene
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