Wednesday, July 11, 2018

Hereditary vs Somatic Mutations July 2018 Chat

Tonight our topic was Hereditary vs Somatic Mutations in gynecologic cancers. Along with our regular participants we also welcomed a few new community members. We especially appreciate the attendance of Erica Bodner (@EMBOSU), a genetic counselor at MD Anderson Cancer Center for sharing her expertise on hereditary mutations and the role of genetic counselors.

You may find a complete transcript here and analytics here. The resources shared during the chat are listed at the end of this post.

Here is a sample of the responses to the questions we asked during the hour chat.

T1: What is the difference between hereditary mutations and somatic mutations?
  • hereditary mutations (aka germline) = changes or "spelling mistakes" in a gene that we inherit from a parent. The mutation is present in every cell of our body. Somatic mutations are what I think of as tumor-specific: changes that occur in the tumor or cancer
  • “When a mutation occurs within germ cells, it is called a germline mutation. Germline mutations affect every cell in an organism and are passed on to offspring. When a mutation occurs in a somatic cell, it is called a somatic mutation.”
  • There are some tricky cases where we look at a tumor for it's somatic mutations and accidentally find hereditary (germline) changes -- since those are in all of the cells, often including the tumor. It can get complicated!
T2: Which gene mutations are known to be associated with hereditary gynecologic cancers?
    • 1) a single gene is like a very long sentence...a mutation=a letter change somewhere within that sentence that causes the sentence to not make any sense to the body. There can be 100s of spots in any given gene that can have a mutation
    • (2): for gyn cancers it's often easier to think about which cancers are linked to which hereditary conditions. Ex: ~3% of endometrial cancers are due to Lynch syndrome (caused by a mutation in 1 of 5 genes: MLH1 MSH2 MSH6 PMS2 or EPCAM)
    • (3) about 10-20% of "epithelial" ovarian cancers are due to a hereditary cause...most often a mutation in BRCA1 or BRCA2, but sometimes can be due to a mutation in a Lynch syndrome gene or a "moderate penetrance" gene like RAD51D
    • Genetic mutation an alteration in DNA occurs after conception ovarian CA inherited mutation in BRCA1/BRCA2
    • Yes. BRCA associated ovarian cancers are more frequently high grade serous carcinomas whereas Lynch syndrome associated ovarian carcinomas are nonserous (most endometrioid or clear cell)
    • BRCA1 and BRCA2
      T3: What testing is needed to find hereditary mutations?
          T3 follow-up... What are the differences between clinical genetic tests and Direct To Consumer (DTC) tests?
          • T3 (1) clinical genetic tests are ordered by your genetic counselor and/or doctor for medical purposes + have high levels of quality control & regulation. DTC labs (historically) have been tests ordered by any1 from home + often used different technology+ non-med purpose
          • 2) now we're starting to see clinical-DTC Hybrids like @Color that are a little bit of both. The genetic testing area is growing & changing very fast...luckily it's our job as genetic counselors to keep track of what's out there & can help navigate you to best options
          • T3: There have been many articles recently about what DTC do and do not cover. Most would need a clinical lab test to confirm results. Genetic counseling key before to decide and after to be sure understand results
          • Evaluation of some direct-to-consumer genetic testing reveals inaccuracies and misinterpretations #gyncsm http://www.facingourrisk.org/XRAYS/inaccurate-dtc-results?utm_source=social&utm_medium=social&utm_campaign=XRAYS%202017-2018%20social%20monitoring
          • Cannot be overemphasized the importance of having ur health care team involved. Confirming DTC results in a clinical laboratory that's well versed in complex variant detection & classification is essential. This is concerning... https://www.nature.com/articles/gim201838
          T4: Do we know what somatic mutations are prevalent in gynecologic cancers?
          • I found this journal article "13 most important genes for gynaecological cancers, being BRAF, CDKN2A, CTNNB1, FBXW7, FGFR2, FGFR3, FOXL2, HRAS, KRAS, NRAS, PIK3CA, PPP2R1A and PTEN." http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0093451
          • Research on somatic mutations is early but is part of the personalized/precision medicine puzzle. BRAF, KRAS, PIK3CA and PTEN have been identified with epithelial ovarian tumors. There are also somatic BRCA mutations. 
           T5: How does knowing you have these mutations impact your healthcare decisions?
            • knowing if you have a hereditary mutation (or not) can impact cancer treatment decision making, cancer screening/prevention options, and can provide info to relatives so they can better understand their cancer risks
            • hereditary mutations can signal risk for other, separate cancers... This can be information to help guide screening and prevention (but the info might also feel like a burden, especially if you are already dealing with one cancer dx).
            • For those already diagnosed, more and more research is coming out to help select the best treatment based on which mutations are present. Genetic and tumor tests can help decide what to try when standard tx doesn't work - or even what to try first.
            • Do you chose prophylactic surgery? Vigilant testing ? #gyncsm. Tough choices
            • Women w/ OC knowing they are BRCA allows for additional treatment options on - PARP for example
            • Knowing that you are at risk for a certain cancers can be powerful information that allows you to take preventative risk reduction measures against developing those cancers
              T6: What role do genetic counselors play in helping patients understand the results of testing?
                • My personal bias is to hope that genetic counselors have good relationships with mental health professionals to refer patients to.
                • Personal risk is discussed. Choices are discussed. Emotional support is discussed. Information is powerful in making best decisions
                • Genetic counseling can be especially important as multi-gene panel might be better suited given your family history (vs testing for one type of mutation).
                • Genetic counselors can help you to navigate and piece together how your cancer history+family history impact your chance to have a hereditary mutation. We can help figure out if the testing you had was hereditary (germline) or somatic.
                • Genetic counselors can help you weigh pro's and con's of genetic testing, and what results could mean for you and your family. Where to get tested? Does insurance cover it? We can help with that too!
                • We can help explain your results, develop a plan for you and your family to help #endcancer. We also want to be a resource - emotional, informational, and for your family. You can find one of us at http://www.nsgc.org @GeneticCouns


                  If you are a patient or caregiver you may continue this discussion on the Smart Patients Platform https://www.smartpatients.com/gyncsm ). 

                  We hope you will join us for the next #gyncsm chat: Wednesday, August 8, 2018 on "What is OK during treatment?" where we'll touch on things like vitamins, supplements, exercise, etc.
                  Have a good month.

                  Dee
                  #gyncsm Co-moderator


                  RESOURCES
                  Germline vs Somatic mutations
                  https://biologywise.com/germline-mutation-vs-somatic-mutation

                  National Society of Genetic Counselors
                  https://www.nsgc.org/

                  FORCE
                  http://www.facingourrisk.org/understanding-brca-and-hboc/getting-tested.php
                  http://www.facingourrisk.org/XRAYS/inaccurate-dtc-results?utm_source=social&utm_medium=social&utm_campaign=XRAYS%202017-2018%20social%20monitoring

                  SGO
                  https://www.sgo.org/newsroom/position-statements-2/genetic-testing-for-gynecologic-cancer/

                  Salon - What Genetic Testing Didn't Tell Me About My Cancer
                  https://www.salon.com/2018/06/24/what-genetic-testing-didnt-tell-me-about-my-cancer/

                  CURE Magazine - Cancer Redefined Personalized Medicine
                  https://www.curetoday.com/community/rick-boulay/2018/07/cancer-redefined-personalized-medicine

                  NATURE - False-positive results released by direct-to-consumer genetic tests highlight the importance of clinical confirmation testing for appropriate patient care
                  https://www.nature.com/articles/gim201838

                  New York Times - The Online Gene Test Finds a Dangerous Mutation...
                  https://www.nytimes.com/2018/07/02/health/gene-testing-disease-nyt.html?nytmobile=0

                  @NIH Fact Sheet
                  https://www.genome.gov/pages/health/patientspublicinfo/genetictestingfactsheet.pdf

                  Designing a High-Throughput Somatic Mutation Profiling Panel Specifically for Gynaecological Cancers
                  http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0093451

                  No comments:

                  Post a Comment