Definition

MSI is an indicator of replication errors accumulating at microsatellite regions as a result of dysfunction in the DNA mismatch repair (MMR) system (MLH1, MSH2, MSH6, PMS2). High MSI (MSI-H) status is associated with a high tumor mutational burden and predicts response to PD-1 inhibitors such as pembrolizumab; MSI-H is found in about 15% of colorectal cancers.

Method

Fragment analysis

Accepted sample types

Fresh tumor tissue, FFPE + Blood (EDTA)

Description

Prior to MMR gene analysis.

Inheritance

Both are possible and the distinction is clinically important, a subset of MSI-H cases (about 3% in colorectal cancer) result from hereditary MMR gene mutations related to Lynch syndrome, while the majority (about 12% in colorectal cancer) are due to sporadic/somatic MLH1 promoter hypermethylation.

Related Tests

Inheritance Patterns

Describes how a genetic condition is passed on within a family. There are five main patterns

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Carrier (Heterozygous / Homozygous)

Why it matters: In autosomal recessive inheritance, when each parent is a carrier (while both appear healthy), the chance of their child being born with the disease is 25% in each

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VUS (Variant of Uncertain Significance)

This is the situation where the test has detected a change in the DNA, but the role of this change in the development of disease is unconfirmed.

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How to Read a Genetic Test Result (Positive / Negative / VUS)

A genetic test result falls into three main categories

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Types of Genetic Tests

A genetic test is a type of medical test that detects changes in genes, chromosomes or proteins. Today there are more than 77,000 genetic tests available.

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