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

Sponsor

Second Affiliated Hospital, School of Medicine, Zhejiang University (Other)

Overall Status

Completed

CT.gov ID

NCT03047226

Collaborator

Guangzhou Burning Rock Medical Examination Institute Co., Ltd. (Industry)

311

Enrollment

Locations

Actual Duration (Months)

44.4

Patients Per Site

2.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lynch Syndrome	Other: next-generation sequencing

Detailed Description

Detect microsatellite instability (by next-generation sequencing and PCR capillary electrophoresis) and germline mutation (by next-generation sequencing) in probands.
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.
Verify the germline mutation in blood relatives whose proband has known likely pathogenic germline mutation or variant of uncertain significance.
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.
Analyze the specificity and the sensitivity of detecting microsatellite instability (MSI) by next-generation sequencing; and analyze the consistency between IHC and MSI.
Analyze the clinical characteristics and germline mutation of Lynch syndrome in Chinese population.

Study Design

Study Type:

Observational

Actual Enrollment :

311 participants

Observational Model:

Case-Only

Time Perspective:

Retrospective

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

Actual Study Start Date :

Feb 28, 2017

Actual Primary Completion Date :

Jul 31, 2018

Actual Study Completion Date :

Jul 31, 2018

Outcome Measures

Primary Outcome Measures

Pathogenic germline mutation [Upon completion of study, on average 2 years.]
Pathogenic germline mutation using next-generation sequencing with a targeted panel.

Secondary Outcome Measures

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fujian Medical University Cancer Hospital	Fuzhou	Fujian	China
2	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong	China
3	Tianjin Medical University Cancer Institute and Hospital	Tianjin	Tianjin	China
4	Yunnan Cancer Hospital	Kunming	Yunnan	China
5	Affiliated Hangzhou First People's Hospital	Hangzhou	Zhejiang	China
6	Zhejiang Cancer Hospital	Hangzhou	Zhejiang	China
7	YUANYING	Hangzhou	Zhejinag	China	310009