Whole-Exome Sequencing (WES) of Intraductal Neoplasms of the Bile Duct (IPNB)

Study Overview
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Brief Summary
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Intraductal papillary neoplasm of the bile duct (IPNB) is a distinct type of biliary tumor characterised with delicate fibrovascular stalks (papillary of villous) covered at biliary epithelium. The typical pathologic feature is dramatical dilation of affected bile ducts due to obstruction by mucin production. IPNB has a better prognosis than bile duct carcinoma, but the current proposed entity contains multiple definitions or categories, thus confused in pathology. Although mutations of several genes on IPNBs (such as GNAS, KRAS, APC, CTNNB1, and RNF43) identified in previous studies, there is still an unification at gene expression signature. This research trial will use whole exome sequencing and subsequent bioinformatic analysis in finding causative mutations in deoxyribonucleic acid (DNA) samples from IPNBs patients.

Detailed Description
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Using production-scale platform, this study will carry out whole exome sequencing from archival (FFPE) material to Identification and classification of significantly mutated genes, determine the somatic genomic alterations that may be relevant to the development or treatment of cancer, establish classification of IPNBs gene mutation signature. Next, analysis of gene mutation signature and IPNBs clinicopathologic outcomes, including the association between pathologic type, long-term oncological outcomes and gene mutation signature. Last, the determination of involved signal pathways at IPNB patients.

Official Title
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Classification of Mutation Characteristics by Whole-Exome Sequencing (WES) in Intraductal Neoplasms of the Bile Duct (IPNB) Patients

Conditions
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Bile Duct Neoplasms, Intraductal Papillary Mucinous Neoplasm

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of IPNBs ECOG Performance status of 0, 1, or 2 Adequate liver function, bilirubin < 1.5 times ULN, ALT or AST < 2.5 times ULN Adequate renal function: creatinine < 1.8 Must be at least 18 Exclusion Criteria: Diagnosis of hepatic mucinous cystadenoma (MCN) Complicated with other Malignancy Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| IPNB<br>intraductal papillary neoplasm of the bile duct | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of novel genetic contributors to IPNBs | Novel genetic abnormalities that are found to be associated with IPNBs via production-scale platform for whole exome sequencing from archival (FFPE) material. The tumor and normal specimens will be obtained from patients with IPNBs who are receiving treatment at Fujian Provincial Hospital, Fujian Medical University Union Hospital and First affiliated Hospital of Fujian Medical University. | 1 year | 
| Validation of WES outcomes | To precise determination of mutation signature of WES results by Sanger Sequencing. | 1 year | 
| Determination of involved signal pathways | To predict and verify the involved signal pathways by bioinformatics | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Whole-exome Sequencing, intraductal papillary neoplasms of the bile duct, mutation characteristics