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Article Open Access

Chromosome 20q gene signature associated with colorectal cancer progression

  • Authors:
    • Jennifer Carter Jones
    • Apurva M. Hegde
    • Yu-Jing Huang
    • Ganiraju Manyam
    • Vibhuti Srivastava
    • Jee Hoon Song
    • Yulan Cheng
    • Ralf Krahe
    • Warapen Treekitkarnmongkol
    • Stephen J. Meltzer
    • Scott Kopetz
    • Stanley R. Hamilton
    • Hiroshi Katayama
    • Subrata Sen
  • View Affiliations / Copyright

    Affiliations: Department of Translational Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA, Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA, Department of Bioinformatics and Computational Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA, Department of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA, Program in Human and Molecular Genetics, The University of Texas Graduate School of Biomedical Sciences, Houston, TX 77030, USA, Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
    Copyright: © Jones et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 121
    |
    Published online on: July 18, 2025
       https://doi.org/10.3892/or.2025.8954
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Abstract

Amplification of human chromosome 20q has been reported as the most frequently recurring genetic abnormality associated with large scale changes in mRNA and protein levels in sporadic colorectal carcinomas. While some studies have found 20q amplification to be consistent between primary and metastatic samples from the same patient with a role in the development of metastasis and worse patient prognosis, others have reported association with improved overall survival for a subset of these patients with colorectal cancer (CRC). To fine map the Minimal Common Regions (MCRs) of amplification on chromosome 20q and identify the candidate genes playing roles in progression of the disease, microarray comparative genomic hybridization analyses of two in vitro cultured CRC liver metastasis cell line model systems was utilized. Microarray expression analysis led to the identification of a candidate gene signature comprising of four genes, BMP7, DNMT3B, UBE2C and YWHAB, residing in the MCRs that were over expressed in CRC cells. By validating our results in a training set of 23 adenocarcinomas (tumors) and five adenomas (polyps) using reverse transcription‑quantitative PCR, as well as analyses of two larger colorectal cancer test data sets derived from 195 The Cancer Genome Atlas and 182 MD Anderson Cancer Center patients with colorectal adenocarcinoma patients, this gene signature was ascertained to be associated with lymph node spread and/or distant metastasis (P<0.05). Previously reported functional studies of the gene signature indicated their involvement in inflammatory and immune response pathways driving CRC progression.
View Figures

Figure 1

High-resolution genomic profile of
chromosome 20 in colorectal cancer metastasis cell line models. (A)
Heat map representation of copy number along chromosome 20 (the
Y-axis measured in Mb from pter to qter) in each of the cell lines
(X-axis). Copy number is represented by color, with green
representing 0 copies, yellow representing 2 copies (normal) and
reds of increasing intensity representing gain of copies. Gain of
part (for SW620) or complete 20q is observed in all cell lines. The
vertical black line along the right side represents the three
minimal common gain intervals, with the boundaries represented by
the black horizontal lines that cross the heat map. Black arrows
represent the position within the intervals of the BAC clones used
as FISH probes in copy number verification experiments. (B, D and
F) Line graph represents the 29–34 Mb interval (B), 40–44 Mb
interval (D) and 53–56 Mb interval copy number in the five cell
lines (KM12C in red, KM12L4A in green, KM12SM in blue, SW480 in
light blue and SW620 in pink). The black arrow indicates position
of the BAC clones used in FISH probes. (C, E and G) FISH analysis
of the indicated cell lines using the probes 1, 2 and 3 shown in B,
D and F respectively. Scale bar, 10 µm. FISH, fluorescence in
situ hybridization.

Figure 2

Heat map representation of copy
number along the q arm of chromosome 20 (the Y-axis measured in Mb)
in tumor and polyp samples along with HCT116 cell line, with
different intensities of blue and red representing copy gain and
copy loss respectively, white representing no copy change and gray
representing no detected signal. The three regions outlined by the
black boxes represent the three minimal common regions of
amplification respectively.

Figure 3

Validation of expression array data
by RT-qPCR. Fold changes of gene signature were compared in six
cell lines, twenty-three tumor and five polyp samples. All assays
were run in duplicate and the relative expression of the selective
genes in terms of fold change in the cancer cell line, tumor and
polyp samples, compared with normal tissue samples was calculated
using the comparative CT (2−ΔΔCq) method, in reference
to the endogenous control to normalize the data, where CT (cycle
threshold) is defined as the number of cycles required for the FAM
signal to cross the threshold in RT-qPCR. ΔCT was calculated by
subtracting the CT values of control gene from the CT values of the
gene of interest. ΔΔCT was then calculated by subtracting the mean
ΔCT of the control samples from the ΔCT of test samples. RT-qPCR,
reverse transcription-quantitative PCR.
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Copy and paste a formatted citation
Spandidos Publications style
Jones JC, Hegde AM, Huang Y, Manyam G, Srivastava V, Song JH, Cheng Y, Krahe R, Treekitkarnmongkol W, Meltzer SJ, Meltzer SJ, et al: Chromosome 20q gene signature associated with colorectal cancer progression. Oncol Rep 54: 121, 2025.
APA
Jones, J.C., Hegde, A.M., Huang, Y., Manyam, G., Srivastava, V., Song, J.H. ... Sen, S. (2025). Chromosome 20q gene signature associated with colorectal cancer progression. Oncology Reports, 54, 121. https://doi.org/10.3892/or.2025.8954
MLA
Jones, J. C., Hegde, A. M., Huang, Y., Manyam, G., Srivastava, V., Song, J. H., Cheng, Y., Krahe, R., Treekitkarnmongkol, W., Meltzer, S. J., Kopetz, S., Hamilton, S. R., Katayama, H., Sen, S."Chromosome 20q gene signature associated with colorectal cancer progression". Oncology Reports 54.4 (2025): 121.
Chicago
Jones, J. C., Hegde, A. M., Huang, Y., Manyam, G., Srivastava, V., Song, J. H., Cheng, Y., Krahe, R., Treekitkarnmongkol, W., Meltzer, S. J., Kopetz, S., Hamilton, S. R., Katayama, H., Sen, S."Chromosome 20q gene signature associated with colorectal cancer progression". Oncology Reports 54, no. 4 (2025): 121. https://doi.org/10.3892/or.2025.8954
Copy and paste a formatted citation
x
Spandidos Publications style
Jones JC, Hegde AM, Huang Y, Manyam G, Srivastava V, Song JH, Cheng Y, Krahe R, Treekitkarnmongkol W, Meltzer SJ, Meltzer SJ, et al: Chromosome 20q gene signature associated with colorectal cancer progression. Oncol Rep 54: 121, 2025.
APA
Jones, J.C., Hegde, A.M., Huang, Y., Manyam, G., Srivastava, V., Song, J.H. ... Sen, S. (2025). Chromosome 20q gene signature associated with colorectal cancer progression. Oncology Reports, 54, 121. https://doi.org/10.3892/or.2025.8954
MLA
Jones, J. C., Hegde, A. M., Huang, Y., Manyam, G., Srivastava, V., Song, J. H., Cheng, Y., Krahe, R., Treekitkarnmongkol, W., Meltzer, S. J., Kopetz, S., Hamilton, S. R., Katayama, H., Sen, S."Chromosome 20q gene signature associated with colorectal cancer progression". Oncology Reports 54.4 (2025): 121.
Chicago
Jones, J. C., Hegde, A. M., Huang, Y., Manyam, G., Srivastava, V., Song, J. H., Cheng, Y., Krahe, R., Treekitkarnmongkol, W., Meltzer, S. J., Kopetz, S., Hamilton, S. R., Katayama, H., Sen, S."Chromosome 20q gene signature associated with colorectal cancer progression". Oncology Reports 54, no. 4 (2025): 121. https://doi.org/10.3892/or.2025.8954
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