scholarly journals Facile profiling of molecular heterogeneity by microfluidic digital melt

2018 ◽  
Vol 4 (9) ◽  
pp. eaat6459 ◽  
Author(s):  
Christine M. O’Keefe ◽  
Thomas R. Pisanic ◽  
Helena Zec ◽  
Michael J. Overman ◽  
James G. Herman ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Single Molecule ◽  
Rapid Assessment ◽  
Suppressor Gene ◽  
Molecular Heterogeneity ◽  
Liquid Biopsies ◽  
Digital Microfluidic ◽  
Colorectal Cancer Patients

This work presents a digital microfluidic platform called HYPER-Melt (high-density profiling and enumeration by melt) for highly parallelized copy-by-copy DNA molecular profiling. HYPER-Melt provides a facile means of detecting and assessing sequence variations of thousands of individual DNA molecules through digitization in a nanowell microchip array, allowing amplification and interrogation of individual template molecules by detecting HRM fluorescence changes due to sequence-dependent denaturation. As a model application, HYPER-Melt is used here for the detection and assessment of intermolecular heterogeneity of DNA methylation within the promoters of classical tumor suppressor genes. The capabilities of this platform are validated through serial dilutions of mixed epialleles, with demonstrated detection limits as low as 1 methylated variant in 2 million unmethylated templates (0.00005%) of a classic tumor suppressor gene,CDKN2A(p14ARF). The clinical potential of the platform is demonstrated using a digital assay forNDRG4, a tumor suppressor gene that is commonly methylated in colorectal cancer, in liquid biopsies of healthy and colorectal cancer patients. Overall, the platform provides the depth of information, simplicity of use, and single-molecule sensitivity necessary for rapid assessment of intermolecular variation contributing to genetic and epigenetic heterogeneity for challenging applications in embryogenesis, carcinogenesis, and rare biomarker detection.

scholarly journals NDST4 Is a Novel Candidate Tumor Suppressor Gene at Chromosome 4q26 and Its Genetic Loss Predicts Adverse Prognosis in Colorectal Cancer

PLoS ONE ◽  
2013 ◽  
Vol 8 (6) ◽  
pp. e67040 ◽  
Author(s):  
Sheng-Tai Tzeng ◽  
Ming-Hong Tsai ◽  
Chi-Long Chen ◽  
Jing-Xing Lee ◽  
Tzu-Ming Jao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Suppressor Gene ◽  
Candidate Tumor Suppressor ◽  
Candidate Tumor Suppressor Gene

scholarly journals Nkx2.5 Functions as a Conditional Tumor Suppressor Gene in Colorectal Cancer Cells via Acting as a Transcriptional Coactivator in p53-Mediated p21 Expression

2021 ◽  
Vol 11 ◽  
Author(s):  
Huili Li ◽  
Jiliang Wang ◽  
Kun Huang ◽  
Tao Zhang ◽  
Lu Gao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Expression Pattern ◽  
Cell Lines ◽  
Suppressor Gene ◽  
Transcriptional Coactivator ◽  
Wild Type ◽  
Mutational Status ◽  
Sw480 Cells

NK2 homeobox 5 (Nkx2.5), a homeobox-containing transcription factor, is associated with a spectrum of congenital heart diseases. Recently, Nkx2.5 was also found to be differentially expressed in several kinds of tumors. In colorectal cancer (CRC) tissue and cells, hypermethylation of Nkx2.5 was observed. However, the roles of Nkx2.5 in CRC cells have not been fully elucidated. In the present study, we assessed the relationship between Nkx2.5 and CRC by analyzing the expression pattern of Nkx2.5 in CRC samples and the adjacent normal colonic mucosa (NCM) samples, as well as in CRC cell lines. We found higher expression of Nkx2.5 in CRC compared with NCM samples. CRC cell lines with poorer differentiation also had higher expression of Nkx2.5. Although this expression pattern makes Nkx2.5 seem like an oncogene, in vitro and in vivo tumor suppressive effects of Nkx2.5 were detected in HCT116 cells by establishing Nkx2.5-overexpressed CRC cells. However, Nkx2.5 overexpression was incapacitated in SW480 cells. To further assess the mechanism, different expression levels and mutational status of p53 were observed in HCT116 and SW480 cells. The expression of p21WAF1/CIP1, a downstream antitumor effector of p53, in CRC cells depends on both expression level and mutational status of p53. Overexpressed Nkx2.5 could elevate the expression of p21WAF1/CIP1 only in CRC cells with wild-type p53 (HCT116), rather than in CRC cells with mutated p53 (SW480). Mechanistically, Nkx2.5 could interact with p53 and increase the transcription of p21WAF1/CIP1 without affecting the expression of p53. In conclusion, our findings demonstrate that Nkx2.5 could act as a conditional tumor suppressor gene in CRC cells with respect to the mutational status of p53. The tumor suppressive effect of Nkx2.5 could be mediated by its role as a transcriptional coactivator in wild-type p53-mediated p21WAF1/CIP1 expression.

scholarly journals GTF2IRD1 on chromosome 7 is a novel oncogene regulating the tumor‐suppressor gene TGFβR2 in colorectal cancer

2019 ◽  
Vol 111 (2) ◽  
pp. 343-355 ◽  
Author(s):  
Sho Nambara ◽  
Takaaki Masuda ◽  
Yuta Kobayashi ◽  
Kuniaki Sato ◽  
Taro Tobo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Suppressor Gene ◽  
Chromosome 7

scholarly journals Growth Factor–Independent 1 Is a Tumor Suppressor Gene in Colorectal Cancer

2019 ◽  
Vol 17 (3) ◽  
pp. 697-708 ◽  
Author(s):  
Min-Shan Chen ◽  
Yuan-Hung Lo ◽  
Xi Chen ◽  
Christopher S. Williams ◽  
Jessica M. Donnelly ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Growth Factor ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Suppressor Gene

Methyltransferase expression and tumor suppressor gene methylation in sporadic and familial colorectal cancer

2015 ◽  
Vol 54 (12) ◽  
pp. 776-787 ◽  
Author(s):  
Emmi I. Joensuu ◽  
Taina T. Nieminen ◽  
Johanna E. Lotsari ◽  
Walter Pavicic ◽  
Wael M. Abdel-Rahman ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Suppressor Gene ◽  
Gene Methylation ◽  
Familial Colorectal Cancer

NTRK3 as a novel tumor suppressor gene in colorectal cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 469-469
Author(s):  
Yanxin Luo ◽  
Andrew Kaz ◽  
Samornmas Kanngurn ◽  
William M. Grady
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Tumor Suppressor ◽  
Cancer Cells ◽  
Tumor Suppressor Gene ◽  
Suppressor Gene ◽  
Aberrant Methylation ◽  
Colon Cancer Cells ◽  
Colon Adenomas ◽  
Colon Cancer Cell Lines

469 Background: Neurotrophin tyrosine kinase receptor 3 (NTRK3) is a receptor tyrosine kinase that has been shown to be an oncogene in breast cancer and possibly in hepatocellular carcinoma. NTRK3 is a trophic dependence receptor, which is a recently described class of receptors that initiate signaling in both the ligand bound and unbound states. Through a genome-wide screen for aberrantly methylated genes, we identified aberrantly methylated NTRK3 as a frequently methylated gene in colon cancer. The aim for the present study is to determine if NTRK3 is an epigenetically silenced tumor suppressor gene in colorectal cancer. Methods: NTRK3 promoter methylation was analyzed in human colon cancer cell lines, normal colon epithelium tissue, colorectal adenomas and colorectal cancers using quantitative methylation-specific PCR and bisulfite sequencing. NTRK3 mRNA and protein expression were studied using quantitative real-time PCR, immunohistochemistry and western blotting respectively. The tumor suppressor function of NTRK3 was examined by assessing the effect of NTRK3 on cell apoptosis, cell migration and in vitro colony formation assays in colon cancer cell lines stably transfected with an NTRK3 expression construct in the presence or absence of NT-3. Results: NTRK3 is methylated in 60% of colon adenomas and in 57% of colorectal cancers. The aberrant methylation of NTRK3 suppresses NTRK3 expression and releases colon cancer cells from NTRK3 mediated apoptosis induced by the expression of NTRK3 in the absence of the ligand NT-3 via the activation of MAPK/ERK pathway. Methylation of NTRK3 also releases colon cancer cells from NTRK3 mediated suppression of motility and anchorage independent growth. The addition of NT3 to colon cancer cells transfected with NTRK3 inhibits the tumor suppressor effects of NTRK3. Conclusions: The aberrant methylation of NTRK3 is likely functionally relevant for colorectal cancer formation as NTRK3 appears to be a conditional tumor suppressor gene in the colon depending on the expression status of its ligand NT-3. NTRK3 is a novel aberrantly methylated conditional tumor suppressor gene that is frequently methylated in colon adenomas and cancers and whose discovery reveals possible novel treatment approaches to colon cancer.

The Ras Effector RASSF2 Is a Novel Tumor-Suppressor Gene in Human Colorectal Cancer

2005 ◽  
Vol 129 (1) ◽  
pp. 156-169 ◽  
Author(s):  
Kimishige Akino ◽  
Minoru Toyota ◽  
Hiromu Suzuki ◽  
Hiroaki Mita ◽  
Yasushi Sasaki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Suppressor Gene ◽  
Human Colorectal Cancer

Germline Epigenetic Silencing of the Tumor Suppressor Gene PTPRJ in Early-Onset Familial Colorectal Cancer

2010 ◽  
Vol 139 (6) ◽  
pp. 2221-2224 ◽  
Author(s):  
Ramprasath Venkatachalam ◽  
Marjolijn J.L. Ligtenberg ◽  
Nicoline Hoogerbrugge ◽  
Hans K. Schackert ◽  
Heike Görgens ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Early Onset ◽  
Suppressor Gene ◽  
Epigenetic Silencing ◽  
Familial Colorectal Cancer
Sign in / Sign up

Export Citation Format

Share Document