Genomic Analysis of Families With a History of Discordant Cancers

Conditions

• Discordant Cancers

Eligibility Criteria

Sex

ALL

Age

18 Years - 100 Years

Healthy Volunteers

Not accepted

Interventions

• WES via Illumina NextSeq 550 sequencing system — GENETIC
  Sequencing will be performed on an Illumina sequencing system
• Blood Draw — DIAGNOSTIC_TEST
  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 — DIAGNOSTIC_TEST
  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 — DIAGNOSTIC_TEST
  Participant will provide a saliva sample which be shipped to University Hospitals Laborator site at room temperature

Study Details

The purpose of this study is to identify novel gene mutations which have contributed to significant personal and family history of cancer. Adults with and without cancer will be accrued to the study. Participants qualify to take part in this research study because someone in their family has been diagnosed with or because they themselves have a cancer diagnosis. 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.

Key Dates

Start date

Nov 17, 2020

Status verified

Aug 2025

Primary completion

Jul 1, 2028

Completion

Jul 1, 2028

Study Design

Enrollment

150 participants (estimated)

Arms

• Arm: 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
• Arm: 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.

Primary Outcome Measure

Number of participants with a family history of 5 or more discordant cancers that have monogenic germline variants identifiable with WES sequencing [ Time Frame: At baseline for an average of 1.5 hours ]

Central Contacts

• Anna Mitchell, MD PhD
  1-800-641-2422
  [email protected]

Locations (1)

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