Microsatellite Instability Use in Mismatch Repair Gene Sequence Variant Classification

Genes

Bryony A. Thompson¹  Amanda B. Spurdle¹ 

[1] Genetics and Computational Biology Department, QIMR Berghofer Medical Research Institute, 300 Herston Road, Brisbane, QLD 4006, Australia; E-Mail:

关键词: lynch syndrome;    variants of uncertain significance;    mismatch repair;    variant classification;    multifactorial likelihood model;   

DOI  :  10.3390/genes6020150

来源: mdpi

【 摘 要 】

Inherited mutations in the DNA mismatch repair genes (MMR) can cause MMR deficiency and increased susceptibility to colorectal and endometrial cancer. Microsatellite instability (MSI) is the defining molecular signature of MMR deficiency. The clinical classification of identified MMR gene sequence variants has a direct impact on the management of patients and their families. For a significant proportion of cases sequence variants of uncertain clinical significance (also known as unclassified variants) are identified, constituting a challenge for genetic counselling and clinical management of families. The effect on protein function of these variants is difficult to interpret. The presence or absence of MSI in tumours can aid in determining the pathogenicity of associated unclassified MMR gene variants. However, there are some considerations that need to be taken into account when using MSI for variant interpretation. The use of MSI and other tumour characteristics in MMR gene sequence variant classification will be explored in this review.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.