1. The Second International Gastrointestinal Cancer Congress
14 - 16 October 2015
The Role of Copy number variation (CNV) in
Colon Cancer
Narjes Khatoun Shabani Sadr , Seyedeh Zohreh Azarshin
Department of Genetics, College of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran
ABSTRACT
Introduction: Colon cancer is the most common type of cancer and major cause of death worldwide. Colon cancer is a world-wide health problem and the second-most dangerous type of cancer, affecting
both men and women. Although the exact pathogenic mechanisms leading to many cancers are unclear, the consensus view is that cancer results from dysregulation of the activity or expression of genes that
control cell growth and differentiation, leading to abnormal cell proliferation. CNVs have been reported in many kinds of cancers, such as colon cancer, and presumably contribute to this dysregulation. These
genetic variants are defined as DNA segments ranging in size from one kilo base to several mega bases among individuals owing to deletion, insertion, inversion, duplication, or complex recombination. The
role of CNVs as risk factors for cancer is currently underappreciated. However, the genomic instability and structural dynamism that characterize cancer cells would seem to make this form of genetic variation
particularly intriguing to study in cancer. Therefore, this article focuses on colon cancer as one of the most important worldwide cancer.
Method: This article is performed by search on electronic databases including: PubMed, sciencedirect and SCOPUS.
Results: CNVs have clearly been shown to have the potential to indirectly influence a healthy individual’s susceptibility to colon cancer, for example by varying the gene dosage of tumour suppressors or
oncogenes. CGH analysis has also shown that CNV associated with colon cancer. A more direct and immediate role of CNV is seen in cancerous cells, which frequently display CNVs that are absent in the
patient’s normal cells in characteristic parts of the genome.
Conclusion: The study of cancer and CNVs is in its infancy but is maturing quickly. In considering the effect of this form of genetic variation on cancer predisposition, cancer gene expression and tumor
genome profiling, there is much to learn from past studies on genomic disorders. With more studies, the potential value of cancer CNVs as novel biomarkers of cancer susceptibility and initiation, and of
cancer progression and metastases, will become apparent.
Key words: colon cancer, Copy number variation, CNV
INTRODUCTION
The copy number variants (also "gene copy number " or CNVs) is the number of copies of a
particular gene in the genotype of an individual.
Copy-number variations (CNVs)—a form of structural variation—are alterations of the DNA of a
genome that results in the cell having an abnormal or, for certain genes, a normal variation in the
number of copies of one or more sections of the DNA.
CNVs correspond to relatively large regions of the genome that have been deleted (fewer than the
normal number) or duplicated (more than the normal number) on certain chromosomes.
This variation accounts for roughly 13% of human genomic DNA and each variation may range
from about one kilo base (1,000 nucleotide bases) to several megabases in size.
Like other types of genetic variation, some CNVs have been associated with susceptibility or
resistance to disease.
CNVs can be categorized into bioallelic or multialleic states.
CONCLUSIONS
The study of cancer and CNVs is in its infancy but is maturing quickly.
In considering the effect of this form of genetic variation on cancer predisposition, cancer
gene expression and tumor genome profiling, there is much to learn from past studies on
genomic disorders.
Denser micro-arrays, next-generation sequencing and integrative informatics analyses
are around the corner and promise to uncover new CNVs.
There are, therefore, many exciting questions to be addressed:
what role do CNVs have in cancer predisposition and how can we use this newly
discovered form of genetic variation to identify those most at risk?
Which cancer-related genes are affected by CNVs and, of these changes, which are both
necessary and sufficient to cause neoplastic growth?
Can incipient cancer cells use these constitutional deletions and duplications to induce or
accelerate tumorigenesis and tumor proliferation?
As these questions are resolved, the potential value of cancer CNVs as novel biomarkers
of cancer susceptibility and initiation, and of cancer progression and metastases, will
become apparent. Whether cancer CNVs offer insight into genes that might be targets for
novel drug development remains to be determined.
REFERENCES
• Roland P Kuiper,Marjolijn JL Ligten berg,Nicoline Hoogerb rugge,and Ad Geurt s van
Kessel. (2010). Germline copy number variation and cancer risk. Current Opinion in
Genetics & Development, 282 – 289.
• Iuliana Ionita-Laza,Angela J . Rogers,, Christoph Lange,, Benjamin A . Raby,Charles
Lee. (2009). Genetic association analysis of copy-number variation (CNV) in human
disease pathogenesis. Genomics 93 , 22-26.
• Tie-Lin Yang, Yan Guo,Christopher J. Papasian and Hong-Wen Deng. (2013). Copy
Number Variation. In Y. G.-W. Tie-Lin Yang, Genetics of Bone Biology and Skeletal
Disease (p.chapter9).
• Dear, P. H. (July 2009). Copy-number variation: the end of the human genome?
Trends in Biotechnology, 448-456.
• Adam Shlien and David Malkin. (16 June 2009). Copy number variations and cancer.
Genome Medicine, 11:: 62.
SEARCH METHOD
This article is performed by search on electronic databases including: PubMed,
sciencedirect and SCOPUS.
RESULTS
Recent evidence shows that the gene copy number can be elevated in cancer cells.
CNVs that are found frequently in the healthy population (common CNVs) are very likely
to have a role in cancer etiology. CNVs have been reported in many kinds of cancers,
such as colon cancer, and presumably contribute to this dysregulation. You can see
CNVs reported for colon cancer in the following table:
a) An example of a bi-allelic CNV that has a 1-copy allele and a 2-copy allele. The reference individual has two 1-copy alleles but 50% of
individuals in this population have a total of three copies of this gene per cell. All bi-allelic CNVs have three genotypes per diploid cell, and in
this case, copy numbers of 2, 3, and 4 per diploid cell. b) An example of a multi-allelic CNV that has a 0, 1, 2 and 3 copy alleles, resulting in six
genotypes in this population. Only the allelic combinations for the three most common genotypes are shown.
The chromosomes containing common cancer CNVs in the human genome are shown, with centromeric regions in red and Giemsa banding
patterns in white, grey or black. Loci are in green if they were found to contain a cancer-related gene that is overlapped or encompassed by a
CNV.
Proposed model for CNVs in tumorigenesis.
A model of copy-number-variable DNA regions in patients with sporadic (top) or inherited (bottom) cancer. We propose that healthy people
maintain a similar low number of CNVs in their genomes (left; black blocks indicate inherited CNVs), whereas those at risk of developing early
onset cancer have an excess of CNVs and a greater overall genomic burden of copy-number-variable DNA (middle; red blocks indicate somatically
acquired CNVs). As a tumor grows, it acquires more copy-number-variable regions, including tumor-specific regions (blue).
gene locus syndrome Cancer type
APC 5q22.2 Adenomatous
polyposis coil, Turcot
syndrome
colorectal
BMPR1A 10q22.3 Juvenile polyposis Gastrointestinal
polyps
CDH1 16q22.1 Familial gastric
carcinoma
Gastric
EPCAM 2p21 Lynch syndrome colorectal
MADH4 18q21.1 Juvenile polyposis Gastrointestinal
polyps
MSH2 2q21 Lynch syndrome colorectal
MSH6 2p16 Lynch syndrome colorectal
NSD1 5q35.3 Sotos syndrome Increased risk of
benign or malignant
tumors, including
neuroblastoma and
gastric carcinoma
PMS2 7p22 Lynch syndrome colorectal
SMAD4 18q21.2 Juvenile polyposis
syndrome
Colon, stomach,
small bowel and
pancreas
Is the CNVs play a role in susceptibility to colon cancer?
Which CNVs are effective colon cancer risk?