11/22/2019 | Press release | Distributed by Public on 11/22/2019 17:31
National Institutes of Health has awarded the comprehensive cancer center with $8.5 million to study Li-Fraumeni Syndrome
DUARTE, Calif. - Persons who inherit Li-Fraumeni syndrome (LFS) have an extremely increased risk of developing cancer. For instance, females with the syndrome have a 50% chance of developing cancer by the age of 30 and a 90% chance over their lifetime; males with the syndrome have a 70% chance of cancer over their lifetime.
LFS was first described 50 years ago, and 30 years ago the syndrome was linked to inheriting a mutation in the TP53 gene. City of Hope scientists and others worldwide have made advances in identifying and treating people with the syndrome, but more work remains to be done.
A new $8.5 million, five-year grant from the National Institutes of Health seeks to advance research and treatment for this serious syndrome, which can cause multiple cancers, including sarcomas, brain and breast tumors, and adrenocortical cancers.
The project, termed LiFTUP (LiFraumeni and TP53 Understanding and Progress), which is co-led by Judy E. Garber, M.D., M.P.H., of Dana-Farber Cancer Institute and Christopher I. Amos, Ph.D., of Baylor College of Medicine, will provide the largest and most comprehensive examination of TP53-associated cancer risk.
Traditionally, clinical TP53 testing was limited to individuals and families who met specific criteria (typically multiple cancers at very young ages). With the introduction of next-generation-based multigene panel testing, which sequences a person's genome faster and is less costly than previous genetic tests, TP53 testing is now performed on large numbers of people who do not meet the syndrome's criteria. However, the testing has also raised concerns about false positives, or a test result that incorrectly indicates the syndrome is present.
That's because blood samples are often used for genetic testing and people may develop TP53 gene mutations in rapidly growing blood cells as they age. Researchers will also examine this group of people to find out why some people in this group develop blood cancers while others do not.
The inherited syndrome is rare. Only about 1,000 children and adults nationwide are included in the Li-Fraumeni Exploration Consortium, and researchers working on this project will also recruit TP53 carriers identified through broader, more agnostic approaches to testing, including commercial genetic testing laboratories, the Geisinger MyCode project, the PROMPT study of individuals with germline mutations and the ORIEN tumor/germline sequencing project.
'Carriers of true germline TP53 mutations may bear the psychological, medical and financial costs of striking personal and family cancer risks, the burden of intensive surveillance, the high risks of cancer deaths at disproportionately young ages and the weight of possibly passing TP53 variants to offspring,' according to the team.
Consequently, a crucial question researchers want to answer is why some people with a TP53 mutation develop cancer while others do not.
'We're looking at thousands of markers across the whole genome to find out if there are patterns that influence why two TP53 carriers with the same mutation have different outcomes,' Weitzel added. 'We will do a clinical and molecular interrogation of the factors that influence the development of cancer.'
'Our hope is that by focusing more research on children and adults with the TP53 mutation, we will be able to take better care of these individuals,' Weitzel said.
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