Genetic Investigation of Cancer Predisposition

Study Overview
=================
Brief Summary
-----------------
Clinical information and samples (blood, saliva, and tumor) will be collected from patients with multiple cancers and/or a family history of cancer as well as from affected and unaffected relatives; samples will be systematically sequenced and evaluated for candidate driver mutations.

Detailed Description
-----------------
Genetic screening will be performed on DNA (and/or RNA) isolated from collected samples from affected individuals by whole exome sequencing or RNA sequencing using in-house pipeline to identify candidate sequence variants. These variants will be tested for segregation with the phenotype in other relatives (affected/unaffected). Candidate variants will be subjected to additional downstream analysis, to be guided by the actual type of gene/variant.

Official Title
-----------------
Genetic Investigation of Cancer Predisposition

Conditions
-----------------
Genetic Predisposition, Cancer

Intervention / Treatment
-----------------
* Genetic: DNA or RNA Sequencing


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Any age Meets at least ONE of the following: Personal history (with documented diagnosis) of cancer before the age of 50 Personal history of more than one primary cancer Documented diagnosis of cancer AND family history of that same cancer type or multiple other cancers that do not fit classical criteria of hereditary cancer syndromes Documented diagnosis of a rare cancer AND family history of rare cancers that do not fit classical criteria of hereditary cancer syndromes There is the same type of cancer in several generations of a family Documented diagnosis of multicentric cancers (e.g bilateral cancers in paired organs, or multifocal cancers in single organs) that usually occur as single lesions when presented sporadically Early onset cancer (before the age of 50, or breast cancer before age 45) AND family history of early onset cancer Capable of providing access to detailed medical records and family history of cancer Exclusion Criteria: Established genetic diagnosis of a known hereditary cancer syndrome that is compatible with the clinical presentation Incarcerated
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Intervention/Treatment |
| --- |
|Genetic: DNA or RNA Sequencing|Samples will be used for whole exome (DNA) or RNA sequencing|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of Rare Genetic Variant | Genetic screen detects a mutation that is likely responsible for tumor development | through study completion- approximately 6-12 months | 
| Identification of somatic (tumor only) mutation | Genetic screen detects a mutation that is likely responsible for tumor development | through study completion- approximately 6-12 months | 
| Identification of Rare Genetic Variant in family members | Genetic screen detects a mutation that is likely responsible for tumor development | through study completion- approximately 6-12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of clinical spectrum of the disease in families | Genetic and clinical analysis reveals clinical features not previously assigned to the disease | through study completion- approximately 6-12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Genetic analysis, Early diagnosis