Lynch Syndrome
Conditions
Keywords
Lynch Syndrome, mismatch repair, microsatellite instability, next-generation sequencing, immunohistochemistry
Brief summary
The purpose of this study is to determine the proportion of patients diagnosed with Lynch syndrome in colorectal cancer patients with the loss of staining by immunohistochemistry (IHC) of any of the mismatch repair (MMR) proteins. Besides, this study aims to test the specificity and the sensitivity of detecting microsatellite instability (MSI) by next-generation sequencing, and to find out the consistency between IHC and MSI in colorectal cancer patients in China. In addition, researchers want to analyze the clinical characteristics and germline mutation of Lynch syndrome in Chinese population.
Detailed description
1. Detect microsatellite instability (by next-generation sequencing and PCR capillary electrophoresis) and germline mutation (by next-generation sequencing) in probands. 2. Analyze the test outcome with clinical and family information to evaluate the germline mutation status preliminarily: likely pathogenic germline mutation, variant of uncertain significance, non-pathogenic germline mutation. 3. Verify the germline mutation in blood relatives whose proband has known likely pathogenic germline mutation or variant of uncertain significance. 4. Diagnose pathogenic germline mutation and non-pathogenic germline mutation based on clinical characteristics, family information and germline mutation test outcomes (including the outcomes of probands and blood relatives). Diagnose Lynch syndrome and the pathogenic germline mutation carriers in the included population. 5. Analyze the specificity and the sensitivity of detecting microsatellite instability (MSI) by next-generation sequencing; and analyze the consistency between IHC and MSI. 6. Analyze the clinical characteristics and germline mutation of Lynch syndrome in Chinese population.
Interventions
Use next-generation sequencing to test germline mutation and microsatellite instability.
Sponsors
Guangzhou Burning Rock Medical Examination Institute Co., Ltd.
Second Affiliated Hospital, School of Medicine, Zhejiang University
Study design
Observational model
CASE_ONLY
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Inclusion criteria
For probands, the inclusion criteria: All of the following four points should be satisfied: * Histological diagnosis of colorectal cancer; * With the loss of staining by immunohistochemistry of any of the mismatch repair (MMR) proteins (MLH1, MSH2, MSH6, PMS2); * With sufficient tumor tissue and normal tissue to test; * Agree to provide basic information, clinical information and family history of cancer information. For probands, the
Exclusion criteria
* With at least one blood relative with known pathogenic germline mutation(s). For blood relatives verifying germline mutation, the inclusion criteria: All of the following three points should be satisfied: * First- to second-degree blood relatives of probands with germline mutation(s). * With Sufficient tumor tissue and normal tissue to test. * Agree to provide basic information, clinical information and family history of cancer information. For blood relatives verifying germline mutation, the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathogenic germline mutation | Upon completion of study, on average 2 years. | Pathogenic germline mutation using next-generation sequencing with a targeted panel. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Variant of uncertain significance of germline mutation | Upon completion of study, on average 2 years. | Variant of uncertain significance of germline mutation using next-generation sequencing with a targeted panel. |
Countries
China
Outcome results
None listed