In this era of cancer genomics, genetic counselors are often tasked with interpreting somatic and germline genetic test results. Within the Cancer SIG, the Somatic Subcommittee focuses on genetic counselors working within the somatic space and aims to create resources for both genetic counselors and patients. A recent survey identified the need for support around clinical decision-making and report interpretation. While some genetic counselors may have access to periodic “somatic case conferences,” many lack other colleagues with whom to discuss cases, and real-time collaboration is not available. Thus, the Somatic Expert Panel was born.
The Somatic Expert Panel includes seven representatives from different specialties and unique areas of expertise: Kristin Zelley, Jaclyn Schienda, Dana Farengo-Clark and Sarah Bannon are clinical genetic counselors (specializing in various indications including pediatric oncology, adult oncology, and hematologic malignancies); Angie Jacobson and Pia Summerour are laboratory genetic counselors (providing commercial and academic expertise); and Carin Espenscheid works in industry (providing expertise in liquid biopsies).
To engage the Somatic Expert Panel, genetic counselors submit cases for feedback related to somatic testing via a virtual “second opinion” service. The experts review cases and then respond, providing guidance, reassurance and answers. To date, the Somatic Expert Panel has responded to over 40 cases nationwide.
When a case is received, one member of the Expert Panel formulates a response and circulates to the group for additional comments. Questions have included: How do I find resources for somatic findings across tumor types? Should additional testing be ordered? Should this somatic finding trigger germline testing?
A recent case example is outlined below:
Request: I was asked by an oncologist if mismatch repair testing should be considered due to a high tumor mutation burden (26 Muts/Mb). The patient was diagnosed with acute lymphoblastic leukemia (ALL) at age 7. There are no Lynch syndrome gene mutations identified on the tumor and MSI was stable. There is no family history of Lynch syndrome cancers. I am seeing the patient to test for a CDKN2A pathogenic variant that was identified on the tumor testing. Is MMR testing something to consider?
Response: There is no set number that is used for high tumor mutation burden (TMB) and it varies across institutions. Compared to GI tumors, melanoma or lung cancers, the TMB of ALL is usually low. This paper (https://pubmed.ncbi.nlm.nih.gov/28681041/) mentions that mutational burden is higher in lymphoid compared to myeloid malignancies. However, the likelihood of Lynch syndrome or CMMRD in the context of high TMB, MSS tumor, and no somatic MMR alterations is very low. We recommend reviewing the list of VUSs (which may be at the end of the report), as sometimes germline pathogenic or likely pathogenic variants are listed as VUSs on somatic-focused reports. If you are going to be testing for CDKN2A, you can always add MMR and POL genes, or a broader gene panel, but yield is likely low. A few other papers that may be of interest include: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356731/ and https://genomemedicine.biomedcentral.com/articles/10.1186/s13073-017-0424-2.
With permission from submitters, queries and responses from the Somatic Expert Panel will evolve into a monthly digest for the Cancer SIG. We hope that by sharing cases, genetic counselors will have resources to feel confident assessing somatic results and providing guidance to patients and oncology providers.