Genomic Analysis of Families With a History of Discordant Cancers
NCT ID: NCT04860453
Last Updated: 2025-09-03
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
150 participants
OBSERVATIONAL
2020-11-17
2028-07-01
Brief Summary
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Participants' DNA and other clinical information will be obtained from a blood sample in order to study the genetic basis of cancer and related complications. All portions in the DNA that code for proteins (i.e., the exome) will be studied. Participant DNA sample and information about family structure and family medical history and ethnic origin may also be collected to better understand this information. Clinical information will be stored and biological samples, including DNA, will be kept for up to three (3) years after collection for future. Ultimately, once identified, the role of the specific genetics changes in the development of inherited cancer(s) will be characterized.
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Detailed Description
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Other affected individuals identified as having five or more relatives with discordant cancers will receive standard of care (SOC) multicancer panel. Families without any mutations identified (with at least a minimum of 2 members with cancer, 1 without) will be considered for additional sequencing as part of this study's primary objective of describing novel inherited cancer syndromes.
If the individual being evaluated in cancer genetics clinic (i.e. index patient) consents and their family members express interest in the study, they will move on to study visit 1. During this visit, pedigree information and medical histories will be explained, consent verified, and individual genetic counselling provided. Individuals will decide whether or not to be notified that incidental findings exist in their genomes.
Lab requisition will be done to facilitate blood draws and DNA extraction/storage and WES analysis will be completed. Any identified monogenic variants of interest will be sent to an industry partner with Clinical Laboratory Improvement Amendments (CLIA)/College of American Pathologists (CAP) certification for validation.
Study visit 2 to be completed within the next 6 months, at which any identified monogenetic variants of interest will be discussed with the participant. Those undergoing Germline High Functional Impact (gHFI) variant counting will be notified if they have more or less than the general population. Appropriate genetic counselling, recurrence risk, and additional clinical referrals will be made as necessary. Participants will be notified with a binary yes/no of any American College of Medical Genetics incidental findings and a routine clinical genetics follow-up appointment will be made
The primary objective of the study is to identify novel gene variants associated with generalized cancer susceptibility that is manifesting as a personal history of multiple primary tumors or a family history of discordant cancers. This will be done through exploratory, research grade (ie NOT CLIA/CAP certified) whole exome sequencing (WES) studies provided to patients/families with family histories of discordant cancers as an adjunct to SOC clinical genetics evaluation in order to clinically describe novel syndromic manifestations of cancer susceptibility. Suspected germline variants supporting a generalized cancer susceptibility will be further validated in a CLIA/CAP certified laboratory prior to being reported out to the patient's medical chart
Conditions
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Study Design
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OTHER
PROSPECTIVE
Study Groups
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Affected participants with 5 or more discordant cancers - WES
Affected individuals with a family history of 5 or more discordant cancers in unilateral descent with a 3-generation pedigree will receive SOC CLIA/CAP multicancer panel (DNA collected via blood draw or punch biopsy) to examine monogenic variant diagnostic yield. Eligible participants (families with no mutations and at least 2 affected and 1 non-affected family members) may move forward with WES.
Any identified monogenic variants of interest will be sent to an industry partner with CLIA/CAP certification for validation. A 6-month follow-up visit will take place during which variants will be discussed and participants who underwent gHFI variant counting (those who were not considered a gene candidate) will have results explained. Appropriate genetic counselling, recurrence risk, and additional clinical referrals will be made as necessary
WES via Illumina NextSeq 550 sequencing system
Sequencing will be performed on an Illumina sequencing system
Blood Draw
Blood draw will be via any University Hospitals Laboratory site and sent at room temperature via courier to the Center for Human Genetics (CHG) Laboratory
Skin biopsy
Skin samples obtained via 3mm punch biopsy will be suspended in cell culture media prepared per CHG routine and sent via courier to the Center for Human Genetics Laboratory
Saliva Sample
Participant will provide a saliva sample which be shipped to University Hospitals Laborator site at room temperature
SOC genetic counseling (routine clinical care)
Affected individuals (cancer) with a family history suggestive of a known hereditary syndrome or meeting NCCN criteria for germline testing will receive SOC CLIA/CAP multicancer panel in order to examine monogenic variant diagnostic yield (retrospective data)
This arm would also include prospective participants from the "5 or more discordant cancers" group who DID have a variant identified and therefore did not move on to WES.
Blood Draw
Blood draw will be via any University Hospitals Laboratory site and sent at room temperature via courier to the Center for Human Genetics (CHG) Laboratory
Skin biopsy
Skin samples obtained via 3mm punch biopsy will be suspended in cell culture media prepared per CHG routine and sent via courier to the Center for Human Genetics Laboratory
Saliva Sample
Participant will provide a saliva sample which be shipped to University Hospitals Laborator site at room temperature
Interventions
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WES via Illumina NextSeq 550 sequencing system
Sequencing will be performed on an Illumina sequencing system
Blood Draw
Blood draw will be via any University Hospitals Laboratory site and sent at room temperature via courier to the Center for Human Genetics (CHG) Laboratory
Skin biopsy
Skin samples obtained via 3mm punch biopsy will be suspended in cell culture media prepared per CHG routine and sent via courier to the Center for Human Genetics Laboratory
Saliva Sample
Participant will provide a saliva sample which be shipped to University Hospitals Laborator site at room temperature
Eligibility Criteria
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Inclusion Criteria
--This cohort is meant as a real world control group receiving routine standard of care and is not eligible for WES.
* Affected patient with a family history of 5 or more discordant cancers in unilateral descent within a 3-generation pedigree.
* Unaffected family members within such kindreds will be eligible for WES as long as a minimum of 2 affected and 1 unaffected family members consent to WES as trial participants.
Exclusion Criteria
* Unable to receive or decline to receive genetic counselling through the telephone, video conference, or in person
* Families known to segregate a previously identified high penetrance cancer susceptibility gene identified through routine medical genetics evaluation are not eligible WES
* Family is not amenable to routine medical genetics SOC genetics evaluation.
18 Years
100 Years
ALL
No
Sponsors
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Case Comprehensive Cancer Center
OTHER
Responsible Party
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Principal Investigators
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Anna Mitchell, MD PhD
Role: PRINCIPAL_INVESTIGATOR
University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
Locations
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University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
Cleveland, Ohio, United States
Countries
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Central Contacts
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Facility Contacts
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Other Identifiers
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CASE13Z20
Identifier Type: -
Identifier Source: org_study_id
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