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Comparative Study
. 2008 Jan;77(1):25-30.

Germline MSH6 mutations are more prevalent in endometrial cancer patient cohorts than hereditary non polyposis colorectal cancer cohorts

Lisa A Devlin  1 , Colin A Graham, John H Price, Patrick J Morrison
Affiliations
Comparative Study

Germline MSH6 mutations are more prevalent in endometrial cancer patient cohorts than hereditary non polyposis colorectal cancer cohorts

Lisa A Devlin et al. Ulster Med J. 2008 Jan.

Abstract

Objective: To determine and compare the prevalence of MSH6 (a mismatch repair gene) mutations in a cohort of families with Hereditary Non-Polyposis Colorectal Cancer (HNPCC), and in an unselected cohort of endometrial cancer patients (EC).

Design: Two patient cohorts participated in the study. A cohort of HNPCC families who were known to the Regional Medical Genetics department, and an unselected cohort of patients with a history of EC. All participants received genetic counselling on the implications of molecular testing, and blood was taken for DNA extraction with consent. All samples underwent sequencing and Multiple Ligation probe analysis (MLPA) for mutations in MSH6.

Populations: DNA from one hundred and forty-three probands from HNPCC families and 125 patients with EC were included in the study.

Methods: Molecular analysis of DNA in all participants from both cohorts for mutations in MSH6.

Outcome measures: Prevalence of pathogenic mutations in MSH6.

Results: A truncating mutation in MSH6 was identified in 3.8% (95% CI 1.0-9.5%) of patients in the endometrial cancer cohort, and 2.6% (95% CI 0.5-7.4%) of patients in the HNPCC cohort. A missense mutation was identified in 2.9% and 4.4% of the same cohorts respectively. No genomic rearrangements in MSH6 were identified.

Conclusion: MSH6 mutations are more common in EC patients than HNPCC families. Genomic rearrangements do not contribute to a significant proportion of mutations in MSH6, but missense variants are relatively common and their pathogenicity can be uncertain. HNPCC families may be ascertained through an individual presenting with EC, and recognition of these families is important so that appropriate cancer surveillance can be put in place.

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Figures

Fig 1
Fig 1
Sequencing analysis showing a truncating mutation c.755 C>G (p.Ser252X) in exon 4 of MSH6
See this image and copyright information in PMC

References

    1. Devlin LA, Price JH, Morrison PJ. Hereditary non-polyposis colon cancer. Ulster Med J. 2005;74(1):14–21. - PMC - PubMed
    1. Devlin L, Morrison PJ. Inherited gynaecological cancer syndromes. Obstetrician Gynaecologist. 2007;9 (in press)
    1. Vasen HF, Wijnen JT, Menko FH, Kleibeuker JH, Taal BG, Griffioen G, et al. Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis. Gastroenterology. 1996;110(4):1020–7. - PubMed
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    1. McCoubrey AS. The use of mechanical bowel preparation in elective colorectal surgery. Ulster Med J. 2007;76(3):127–30. - PMC - PubMed

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