Germline variants discovered in lymphoma patients undergoing tumor profiling: a case series

Clinical tumor sequencing protocols often depend on obtaining germline DNA from patients to aid in the identification of de novo variants in the tumor, and therefore come with the possibility for the incidental discovery of germline variants. Ninety-one adult patients with lymphoma were consented and enrolled in MIONCOSEQ, an IRB-approved tumor profiling protocol that utilizes an exome sequencing platform. Charts were retrospectively reviewed for germline variants from sequencing results, personal and/or family history of cancer and genetic counseling referral. After review of the 91 lymphoma cases, seven (8%) cases revealed germline variants. Only one of these, CHEK2 p.I157T, has been previously recovered as a germline variant in lymphoma. Two of the seven patients received genetic counseling, two died before genetic counseling could be arranged and three did not follow-up with a genetics provider. None of the patients had a personal or family history that would have otherwise suggested an indication for cancer genetics referral, especially notable as lymphoma is not traditionally associated with inherited cancer syndromes. Importantly, as only two of seven patients had appropriate genetic counseling for their variant, timely genetic counseling should be a critical part of all tumor profiling platforms that use non-tumor DNA.

Automated summary

Clinically, it is common practice to obtain germline DNA from patients for tumor sequencing to identify de novo variants, which could incidentally lead to the discovery of germline variants. In a study involving 91 lymphoma patients, 8% were found to have germline variants, with only one previously identified in lymphoma. Despite this, only two patients received genetic counseling, highlighting the need for timely genetic counseling for all tumor profiling platforms using non-tumor DNA.