Hereditary nonpolyposis colorectal cancer: pitfalls in deletion screening in MSH2 and MLH1 genes.

Eur J Hum Genet 2005 Aug;13(8):983-6

Institute of Human Genetics, University of Bonn, Germany.

Hereditary nonpolyposis colorectal cancer (HNPCC) is caused by a deficiency in DNA mismatch repair in consequence of germline mutations mainly in the genes MSH2 and MLH1. Around 10% of patients suspected of HNPCC are identified with large genomic deletions that cannot be detected by conventional methods of mutation screening. The recently developed multiplex ligation-dependent probe amplification (MLPA) proved to be an easy to perform method for deletion detection and is reliable when more than one exon is deleted. We show that, in some cases, apparent deletions of single exons may actually result from single base substitutions or small insertions/deletions in the hybridisation sequence of MLPA probes. We conclude that single exon deletions, detected by MLPA or multiplex PCR, should be validated with additional methods.

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http://www.nature.com/articles/5201421
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http://dx.doi.org/10.1038/sj.ejhg.5201421DOI Listing
August 2005
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References

(Supplied by CrossRef)

HF Vasen et al.
Gastroenterology 1999

HT Lynch et al.
N Engl J Med 2003

J Wijnen et al.
Nat Genet 1998

JP Schouten et al.
Nucleic Acids Res 2002

Y Wang et al.
Hum Mutat 2002

F Charbonnier et al.
Cancer Res 2000

F Charbonnier et al.
Cancer Res 2002

Y Wang et al.
Int J Cancer 2003

JJ Gille et al.
Br J Cancer 2002

CF Taylor et al.
Hum Mutat 2003

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