A review on the molecular diagnostics of Lynch syndrome: a central role for the pathology laboratory

作者：van Lier Margot G F; Wagner Anja; van Leerdam Monique E; Biermann Katharina; Kuipers Ernst J; Steyerberg Ewout W; Dubbink Hendrikus Jan; Dinjens Winand N M^*

来源：Journal of Cellular and Molecular Medicine, 2010, 14(1-2): 181-197.

DOI：10.1111/j.1582-4934.2009.00977.x

• Lynch syndrome
• mismatch repair genes
• MSI analysis
• immunohistochemistry
• MLH1 promoter methylation assay
• BRAF mutation analysis
• molecular pathology
• review

Lynch syndrome
Identification of patients at risk for Lynch syndrome
Molecular basis of Lynch syndrome and sporadic MMR-deficient tumours
Molecular diagnostics of Lynch syndrome
Description of molecular analyses
MSI analysis
Immunohistochemistry
MLH1 promoter hypermethylation assay
BRAF mutation analysis
Limitations of molecular analyses
Conclusions
Lynch syndrome (LS) is caused by mutations in mismatch repair genes and is characterized by a high cumulative risk for the development of mainly colorectal carcinoma and endometrial carcinoma. Early detection of LS is important since surveillance can reduce morbidity and mortality. However, the diagnosis of LS is complicated by the absence of a pre-morbid phenotype and germline mutation analysis is expensive and time consuming. Therefore it is standard practice to precede germline mutation analysis by a molecular diagnostic work-up of tumours, guided by clinical and pathological criteria, to select patients for germline mutation analysis. In this review we address these molecular analyses, the central role for the pathologist in the selection of patients for germline diagnostics of LS, as well as the molecular basis of LS.

• 出版日期2010-2