Diagnosis of Lynch Syndrome Based on Next-generation Sequencing in Colorectal Cancer

Lynch Syndrome Clinical Trial

Official title:

Diagnosis of Lynch Syndrome Based on the Colorectal Core™ Platform in Colorectal Cancer Patients With the Loss of Staining by Immunohistochemistry (IHC) of Any of the Mismatch Repair (MMR) Proteins: An Open-label and Multi-center Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03047226
• Other study ID #: RSKY2016019
• Status: Completed
• Start date: February 28, 2017
• Est. completion date: July 31, 2018

Study information

• Verified date: July 2021
• Source: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 311
• Est. completion date: July 31, 2018
• Est. primary completion date: July 31, 2018
• Gender: All
• Age group: N/A and older

Eligibility

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 exclusion criteria:

• Blood relatives who refuse to test.

Related Conditions & MeSH terms

• Colorectal Neoplasms, Hereditary Nonpolyposis
• Lynch Syndrome
• Syndrome

Intervention

Other:
• next-generation sequencing
Use next-generation sequencing to test germline mutation and microsatellite instability.

Locations

Country	Name	City	State
China	Fujian Medical University Cancer Hospital	Fuzhou	Fujian
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong
China	Affiliated Hangzhou First People's Hospital	Hangzhou	Zhejiang
China	YUANYING	Hangzhou	Zhejinag
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Yunnan Cancer Hospital	Kunming	Yunnan
China	Tianjin Medical University Cancer Institute and Hospital	Tianjin	Tianjin

Sponsors (2)

Lead Sponsor	Collaborator
Second Affiliated Hospital, School of Medicine, Zhejiang University	Guangzhou Burning Rock Medical Examination Institute Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathogenic germline mutation	Pathogenic germline mutation using next-generation sequencing with a targeted panel.	Upon completion of study, on average 2 years.
Secondary	Variant of uncertain significance of germline mutation	Variant of uncertain significance of germline mutation using next-generation sequencing with a targeted panel.	Upon completion of study, on average 2 years.