Licensed Genetic Counselor University of Utah Huntsman Cancer institute What is Li Fraumeni syndrome Inherited condition which cause an increased risk for developing cancer First described by Dr Fredrick Pei Li and Dr Joseph ID: 929677
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Slide1
Li-Fraumeni Syndrome
Wendy Kohlmann, MS, CGC
Licensed Genetic Counselor
University of Utah
Huntsman Cancer institute
Slide2What is Li-Fraumeni syndrome
Inherited condition which cause an increased risk for developing cancer
First described by Dr. Fredrick Pei Li and Dr. Joseph
FraumeniCaused by mutations in the TP53 geneInherited equally by men and womenWhen a parent has a TP53 mutation, there is a 50% (1 in 2) chance to pass this on to children
Slide3Why would someone be offered genetic testing for Li-Fraumeni
syndrome?
Because a family member has been found to have a TP53 mutation
When a TP53 mutation is identified in a person, it is generally recommended that relatives be tested to determine if anyone else has inherited this and is at riskBecause your doctor suspects that you may have Li-Fraumeni syndromeCertain types of cancer or patterns of cancer can raise concerns about a TP53 mutation. Genetic testing may be recommended to determine the cause of the cancer.
Determining whether cancer is due to Li-
Fraumeni
syndrome may help with planning treatment and screening for future cancer
Slide4Genetic testing for Li-Fraumeni syndrome
Genetic testing of the TP53 gene is recommended for the following:
Choroid plexus tumors
Adrenocortical tumorsRhabdomyosarcoma-embryonal anaplastic subtype Individual with multiple Li-Fraumeni related cancers before age 46 An individual with a Li-
Fraumeni
related cancer before age 46 and a close relative (parent, sibling, children, aunt, uncle, grandparent) with a Li-
Fraumeni
related cancer before age 56
*Classic Li-
Fraumeni
cancers include adrenocortical tumors, breast cancer, osteosarcomas, soft tissue sarcomas, brain tumors
Slide5Sometimes TP53 is included in other genetic tests
Genetic testing technology allows for many genes to be tested at once
TP53 is now included in many genetic tests for various cancer risks
When having genetic testing, it is important to ask why your doctor or genetic counselor:Why they think the testing would be helpfulWhat genes are being testedWhat are the possible outcomes
Slide6What if I decide not to have genetic testing?
Having genetic testing is a personal choice
Without information from genetic testing, recommendations can be made on the basis of family history
However, it can be difficult to identify those families who have Li-Fraumeni syndrome based on family history alone Invasive procedures (ex. risk reducing mastectomies) or specialty screening exams (ex. whole body MRI) it may be difficult to obtain without a confirmed diagnosis
Slide7What does it mean when a variant of uncertain significance is found in TP53?
All people have differences in our DNA
Not all variations in the genetic code are bad!
Some have no effectSome contribute to unique featuresSome cause a gene to not function and cause an increased risk for diseaseWhen a laboratory does not have enough information about a particular genetic variant to determine its effect, it will report the finding as uncertain
When this finding occurs
Discuss with a genetic counselor or genetic specialist
Other laboratories may know more about variant
Find out how you will be notified when more is learned about the variant
Ask about research
Slide8What is mosacism?
Detecting a TP53 mutation on a genetic test does not always mean a person has Li-Fraumeni syndrome
TP53 Mutations
can arise in the blood as we get older or as an effect of chemotherapyThese mutations do not cause an increased risk for cancer in other parts of the bodyThey cannot be passed on to children
They may indicate some risk for developing hematologic malignancy
In rare cases a person may be mosaic for a TP53 mutation, meaning that the mutation arose some time after fertilization as the embryo developed. The mutation is only present in some cells in the body. In this situation, there can be risks for other cancers and there is a possibility of passing on the mutation to children depending on which tissues are affected.
When a TP53 mutation is identified for the first time in a family, steps should be taken to determine if the mutation is truly present in all cells (causing Li-Fraumeni syndrome) or if it may have been detected for other reasons.
Slide9How does cancer treatment change for someone with Li-Fraumeni
syndrome?
Must do what is best to treat the current cancer!
If there are equally good options for treating a cancer, then choosing treatments that are less likely to cause a risk for additional cancers can be chosenExample: treating breast cancer with a mastectomy rather than lumpectomy and radiation
Slide10How does treatment change for someone with Li-Fraumeni syndrome?
Unaffected people or people not currently being treated for cancer can benefit from comprehensive screening to identify cancers at the earliest possible stage
Kratz
et al.
Clin
Canc
Research 2017
Slide11Kratz
et al.
Clin
Canc Research 2017
Slide12What can a genetic counselor do for you?
Help coordinate and interpret genetic testing
Provide support and facilitate adjustment to this diagnosis
Present cancer screening programs Educate other providers on the care team about LFS and facilitate communicationProvide information and referrals to support resourcesFacilitate sharing information with family membersPresent information in an age and developmentally appropriate ways
Provide updates on new research and developments
Discuss reproductive planning options
Identify research options
Slide13How do I find a genetic counselor?
National Society of Genetic Counselors
Find a genetic counselor tool: https
://www.nsgc.org/
Slide14Huntsman Cancer Institute Cancer Genetics Study
Registry of patients with hereditary cancers including Li-
Fraumeni
syndromeParticipation involves:Allowing access to medical, family history and genetic testing dataProviding blood samplesTracking outcomes of screeningContact information:Sara Johnson, at 801-585-7343 or at
cgs@hci.utah.edu
http://healthcare.utah.edu/huntsmancancerinstitute/research/research-studies/cancer-genetics-study/
Slide15What do elephants have to do with Li-Fraumeni syndrome?
Estimated 4-5% risk for cancer
40 copies of TP53
Approximately 25% risk for cancer
2 copies of TP53
Elephants
Human
Slide16Elephants
When exposed to damaging radiation, elephant
cells more likely to self-destruct
than human cells Research is now ongoing to develop approaches for delivering elephant TP53 to cells and to see test the effect of elephant TP53 in human cancer cellsCollaborating with a chemical engineer in Israel to put elephant TP53 into Nano particles that allow the pieces of DNA to be delivered to cellsStill a ways away from being used to treat people
Slide17Other resources
NIH Li-
Fraumeni
study: Provides screening services https://lfs.cancer.gov/participation.htmlPROMPT STUDY: Trying to learn more about TP53 mutations found through multigene testing http://promptstudy.info/
Find My Variant:
Researching
uncertain variants
https://findmyvariant.org
/
Living with LFS and LFS Association: Meet others, get involved
Resources for mindfulness: Calm
,
Buddhify
, Headspace