Clinical trial NCT03047226: Diagnosis of Lynch Syndrome Based on Next-generation Sequencing in Colorectal Cancer
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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Lynch Syndrome
Keywords: Lynch Syndrome
mismatch repair
microsatellite instability
next-generation sequencing
immunohistochemistry
Lead sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
Sponsor class: OTHER
Collaborators: name: Guangzhou Burning Rock Medical Examination Institute Co., Ltd.
First posted: 2017-02-08
Enrollment: 311
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Observational model: CASE_ONLY
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The probands will be selected from colorectal cancer patients with the loss of staining by immunohistochemistry of any of the mismatch repair (MMR) proteins (MLH1, MSH2, MSH6, PMS2).

The blood relatives verifying germline mutation will be selected from whose probands have germline mutation(s).

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.

Eligibility 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 exclusion criteria:

* Blood relatives who refuse to test.

Primary outcomes:
measure: Pathogenic germline mutation
timeFrame: Upon completion of study, on average 2 years.
Secondary outcomes:
measure: Variant of uncertain significance of germline mutation
timeFrame: Upon completion of study, on average 2 years.
Other outcomes:
Locations:
city: Fuzhou
country: China
facility: Fujian Medical University Cancer Hospital
state: Fujian
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
city: Kunming
country: China
facility: Yunnan Cancer Hospital
state: Yunnan
city: Hangzhou
country: China
facility: Affiliated Hangzhou First People's Hospital
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
city: Hangzhou
country: China
facility: YUANYING
state: Zhejinag
Study officials:
affiliation: Second Affiliated Hospital, School of Medicine, Zhejiang University
name: Ying Yuan, MD
role: PRINCIPAL_INVESTIGATOR
References: