Next Article in Journal
Sequencing of Bacterial Genomes: Principles and Insights into Pathogenesis and Development of Antibiotics
Next Article in Special Issue
Lynch Syndrome: An Updated Review
Previous Article in Journal
Monogenic Diabetes: A Diagnostic Algorithm for Clinicians
Previous Article in Special Issue
Abnormal Base Excision Repair at Trinucleotide Repeats Associated with Diseases: A Tissue-Selective Mechanism
Genes 2013, 4(4), 536-555; doi:10.3390/genes4040536

Copy Number Variation in Hereditary Non-Polyposis Colorectal Cancer

1,2, 1,2
Received: 26 July 2013 / Revised: 2 September 2013 / Accepted: 11 September 2013 / Published: 26 September 2013
(This article belongs to the Special Issue Microsatellite Instability)
View Full-Text   |   Download PDF [593 KB, uploaded 26 September 2013]   |   Browse Figure


Hereditary non-polyposis colorectal cancer (HNPCC) is the commonest form of inherited colorectal cancer (CRC) predisposition and by definition describes families which conform to the Amsterdam Criteria or reiterations thereof. In ~50% of patients adhering to the Amsterdam criteria germline variants are identified in one of four DNA Mismatch repair (MMR) genes MLH1, MSH2, MSH6 and PMS2. Loss of function of any one of these genes results in a failure to repair DNA errors occurring during replication which can be most easily observed as DNA microsatellite instability (MSI)—a hallmark feature of this disease. The remaining 50% of patients without a genetic diagnosis of disease may harbour more cryptic changes within or adjacent to MLH1, MSH2, MSH6 or PMS2 or elsewhere in the genome. We used a high density cytogenetic array to screen for deletions or duplications in a series of patients, all of whom adhered to the Amsterdam/Bethesda criteria, to determine if genomic re-arrangements could account for a proportion of patients that had been shown not to harbour causative mutations as assessed by standard diagnostic techniques. The study has revealed some associations between copy number variants (CNVs) and HNPCC mutation negative cases and further highlights difficulties associated with CNV analysis.
Keywords: microsatellite instability (MSI); cancer; DNA repair; diagnostic testing; HNPCC/Lynch Syndrome; copy number variation; affymetrix; array microsatellite instability (MSI); cancer; DNA repair; diagnostic testing; HNPCC/Lynch Syndrome; copy number variation; affymetrix; array
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Share & Cite This Article

Further Mendeley | CiteULike
Export to BibTeX |
MDPI and ACS Style

Masson, A.L.; Talseth-Palmer, B.A.; Evans, T.-J.; Grice, D.M.; Duesing, K.; Hannan, G.N.; Scott, R.J. Copy Number Variation in Hereditary Non-Polyposis Colorectal Cancer. Genes 2013, 4, 536-555.

View more citation formats

Related Articles

Article Metrics

For more information on the journal, click here


Cited By

[Return to top]
Genes EISSN 2073-4425 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert