Genomic Structural Variation in Cancer Susceptibility

November 3, 2025 updated by: Memorial Sloan Kettering Cancer Center

This study will look for new types of gene changes that may be related to cancer in some patients. Some gene changes (mutations) are passed on from parents to offspring (child). Other gene changes are new and are seen for the first time in a child. They are not seen in the parent.

Some of these gene changes may cause cancers in the offspring. We will look for gene changes by studying patients with cancer their parents and family members without cancer. In this study, we will be able to find gene changes that occur in the cancer patient but not in the rest of the family. Knowing the role that new gene changes play in cancer risk may help us find people at a higher risk of getting cancer.

Study Overview

Status

Active, not recruiting

Conditions

Study Type

Observational

Enrollment (Actual)

1275

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

United States
- New York
  - New York, New York, United States, 10065
    - Memorial Sloan Kettering Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

Child
Adult
Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

The majority of eligible probands will be identified prospectively through the clinics of the Clinical Genetics, Medical Oncology and Pediatric Oncology Services of MSKCC by the patient's physician, the protocol investigator, or a research team member.

Description

Inclusion Criteria:

Proband must have living unaffected biologic mother and father available and eligible for participation in the study with one of the following (both incident and prevalent cases will be collected):
- Colorectal cancer diagnosed at or under the age of 50.
- Breast cancer diagnosed at or under the age of 45.
- Germ cell tumor diagnosed at or under the age of 40.
- Pediatric cancer of any type diagnosed at or under the age of 21
- Adult cancer or pre-neoplastic condition of any type diagnosed at or under the age of 40
- Cancer at any age in 2 or more siblings suggestive of a genetic etiology, such as brothers with testicular germ cell tumor or sisters with breast cancer and ovarian cancer
Parents:
- Must be the biologic mother and biologic father of affected proband.
- Must have (by self-report) no history of cancer other than non-melanomatous skin cancer or cervical cancer in situ except in the case of inclusion criteria #6..
- In certain clinical situations, parent(s) with cancer may be included at the discretion of the Principal Investigator, if the Principal Investigator deems that the etiology of cancer in the parent(s) and proband are biologically unrelated.
Sibling(s):
- Must be age 18 or older and have same biologic parents as proband.

Exclusion Criteria:

Known genetic mutation in proband or a family history that is indicative of hereditary cancer susceptibility.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Observational Models: Family-Based
Time Perspectives: Other

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To determine the frequency of de novo germline copy number variants (CNVs) in cancer affected probands using an ascertainment of "trios" consisting of cancer patients and their unaffected biologic parents Time Frame: 2 years	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To explore the role of germline homozygosity in cancer susceptibility by determining the frequency and length of autozygous regions in patients with cancer Time Frame: 2 years	and mechanisms of Mendelian inheritance, such as autosomal recessive, autosomal dominant, and X-linked, which upon initial ascertainment may be difficult to decipher.	2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

Weill Medical College of Cornell University

Cold Spring Harbor Laboratory

Coriell Institute

University of Washington Center for Mendelian Genomics

Investigators

Principal Investigator: Zsofia Stadler, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Memorial Sloan-Kettering Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2009

Primary Completion (Estimated)

October 1, 2026

Study Completion (Estimated)

October 1, 2026

Study Registration Dates

First Submitted

October 15, 2009

First Submitted That Met QC Criteria