Finding Cancer Susceptibility Genes & Assessing Unclassified Sequence Variants

Research in the Tavtigian Lab concentrates on two areas of genetic susceptibility to cancer:

  1. Identification and characterization of intermediate-risk and high-risk cancer susceptibility genes.
  2. Analysis of unclassified variants that are observed during the clinical testing of established high-risk cancer susceptibility genes.

Historically, most of the known high-risk cancer susceptibility genes were found either by linkage analysis/positional cloning or by mutation screening of established high-risk susceptibility genes' biochemical pathway "nearest neighbors."

New Strategies for Gene Identification

While the linkage analysis/positional cloning approach is nearly obsolete, next-generation sequencing enables a number of new strategies for gene identification. One of these is whole-exome mutation screening in pedigrees as a method to identify relatively high-risk susceptibility genes. Another is biochemical pathway–based mutation screening in a case-control format as a method to identify intermediate-risk susceptibility genes. We are pursuing breast cancer genetics projects in both of these areas and are likely to expand to prostate cancer or colon cancer projects in the near future.

UVs: Unclassified Sequences Variants

Clinical mutation screening of high-risk cancer susceptibility genes such as BRCA1, BRCA2, MLH1, and MSH2 will often find clearly pathogenic mutations, providing very useful information for the clinical management of high-risk patients and their close relatives. However, about 10% of patients who undergo mutation screening are found to carry an unclassified sequence variant (UV). Observations of UVs are problematic for clinical mutation screening services, for clinical cancer genetics, and for the patients.

We have developed a bioinformatics method, called the "integrated evaluation," for analysis and eventual classification of UVs. Currently, the method is applicable to UVs in the breast cancer susceptibility genes BRCA1 and BRCA2. We are working to improve the method, to extend it to other susceptibility genes, and to create databases that will disseminate classification results to clinical cancer geneticists throughout the world.

News & Blog

Huntsman Cancer Institute Researchers Share Expertise at National Cancer Meeting
Health Care Transformation, Clinical, Research, Education
Apr 11, 2017

Huntsman Cancer Institute Researchers Share Expertise at National Cancer Meeting

Huntsman Cancer Institute,

More than 20 researchers from Huntsman Cancer Institute (HCI) at the University of Utah made their mark on the American Association of Cancer Research (AACR) Annual Meeting this year. Held in Washington, D.C., the convention drew more than 21,500 cancer researchers from all over the world. Scientists attended sessions on topics from immunotherapy to precision medicine. About 15 researchers from HCI presented posters in the main conference hall, on a wide range of topics. ... Read More

Genetic Test Results for Lynch Syndrome Improved with New Computer Program
Research
Oct 31, 2012

Genetic Test Results for Lynch Syndrome Improved with New Computer Program

Huntsman Cancer Institute,

Many patients who have genetic testing for Lynch syndrome, a hereditary predisposition to colon cancer, receive the inconclusive result "variants of uncertain clinical significance." This can be a problem, as people with Lynch syndrome have a much higher probability to develop colon cancer, and often develop colon cancer at an earlier age than is common among the general population; consequently, they need to begin screening at a much younger age.... Read More

Sean Tavtigian
Sean V. Tavtigian, PhD
Principal Investigator
sean.tavtigian@hci.utah.edu
Cancer Center Bio

Contact Us

Lab related:
Judith RosenthalTechnician
jude.rosenthal@hci.utah.edu

For everything else, please contact:
Sean V. Tavtigian, PhD
sean.tavtigian@hci.utah.edu