Inherited mutations in the BRCA1 gene can significantly increase a person’s risk of breast and ovarian cancer—but not every mutation is harmful. Researchers from Huntsman Cancer Institute evaluated hundreds of different mutations and in a published study, Sean Tavtigian, PhD, explains how this information can be used to better understand and manage individual cancer risk.... Read More
Finding Cancer Susceptibility Genes & Assessing Unclassified Sequence Variants
Research in the Tavtigian Lab concentrates on two areas of genetic susceptibility to cancer:
- Identification and characterization of intermediate-risk and high-risk cancer susceptibility genes.
- 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
A new research initiative at Huntsman Cancer Institute at the University of Utah builds upon Utah’s history of genetic discovery to inform strategies that help affected families reduce their cancer risk. Called the Center for Cancer Genetics at HCI, its initial work includes two statewide projects designed to advance understanding of genetic predisposition of cancer and other disease.... Read MoreSurgery
An international team of researchers led by Huntsman Cancer Institute at the University of Utah has developed, calibrated, and validated a novel tool for identifying the genetic changes in Lynch syndrome genes that are likely to be responsible for causing symptoms of the disease. The results were published in the journal Genetics in Medicine. ... Read More
Researchers developed a new mathematical tool to validate and improve methods used by medical professionals to interpret results from clinical genetic tests. The work was published this month in Genetics in Medicine.... Read More
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