EducateNext: How to Interpret Unclear Genetic Data (Familial GI Cancer Syndromes)

  • The rapid progress in genetic testing has been gratifying because it provides the efficient discovery of the genetic basis of many familial clusters of cancer—specifically gastrointestinal cancer for the purposes of this lecture. However, we are a long way from a complete understanding of which genes confer what degree of cancer risk.

    This lecture will introduce the main problems, which are how to deal with variants of uncertain significance, how to deal with unexpected genetic results, the failure to find a genetic explanation for what seems to be a genetic disease, and phenocopies.

    A substantial portion of the lecture will address the fact that CRC is actually a cluster of diseases in which every tumor is different at a genetic level, but many of the tumors can be placed into general pathogenetic categories (chromosomal instability - CIN, microsatellite instability – MSI, and CpG Island Methylator Phenotype - CIMP). There will be a detailed discussion of the somatic mutations in CRCs, both in terms of the general number and types of mutations. An important point is that cancers are all caused by mutations, but the sequence variations detected in a tumor can be the drivers of neoplastic cellular behavior or alternatively, innocent bystanders or passengers. The techniques used to categorize CRCs into common classes include testing for MSI and immunohistochemistry, which provides some insight into the mechanisms driving the tumor. The actual target mutations that are driving CRCs with MSI will be discussed. Finally, some challenges in characterizing or classifying mutations will be described, including the problem of innocent sequence variants linked to the real but possibly undetected germline mutation, and the vexing issue of phenocopies.



C. Richard (Rick) Boland was a graduate of Notre Dame and Yale Medical School. He wrote an MD thesis in 1973 on work done on a poorly characterized familial cancer syndrome that we now call Lynch Syndrome, and has focused his research career on basic and genetic aspects of colorectal cancer (CRC). He has been funded by the multiple agencies (NIH, VA, Foundations) continuously since 1979, and published about 400 articles.

Rick’s fellowship and academic career began at UCSF (1978-84) under the mentorship of Young S. Kim, MD, where he focused his research on cancer-related glycoprotein biochemistry. From 1984-95, he was on the faculty of the University of Michigan eventually becoming a full Professor; in 1990, he undertook a sabbatical with Andy Feinberg at Michigan to redirect his research to tumor genetics. In 1995, Rick was recruited to UCSD as Division Chief in GI. From 2003 to 2014, his research career was at Baylor University Medical Center in Dallas, where he primarily focused upon his laboratory and clinical work in tumor genetics in collaboration with Ajay Goel, PhD.

Rick has been closely aligned with the AGA over his career, and has served on numerous committees, chairing several, was Associate Editor of Gastroenterology (1991-96), and AGA President in 2011-12. He has been honored with several AGA awards including the Funderburg Award, the Beaumont Prize for research, and the Friedenwald Medal for contributions to gastroenterology. He was honored by the GI Oncology Section with the Distinguished Mentor Award in 2011; two of his trainees are currently Department Chairs at Michigan and Stanford, and 5 have held endowed chairs. He was honored by the Collaborative Group of the Americas on Inherited Colorectal Cancer with their Lifetime Achievement Award. He has been a frequent member of NIH Study Sections and Chaired the CIMG Study Section from 2014-6.


Kory Jasperson, MS, CGC is a Board-certified senior genetic counselor at Ambry Genetics. He has over 10 years of clinical cancer genetics experience and also completed a cancer genetics fellowship at City of Hope. Mr. Jasperson co-founded the Lynch Syndrome Screening Network (LSSN) and was previously Vice-Chair of both the Hereditary Colon Cancer Foundation and two National Comprehensive Cancer Network (NCCN) guidelines. Mr. Jasperson has over 50 research publications, many of which involve hereditary gastrointestinal cancers.

Register Now
  • Mon, April 2, 2018
  • 12:00pm PDT
  • Duration: 1 hour
  • C.E.U. 1 unit
  • P.A.C.E. 1 unit

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