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

Fam Cancer. 2021 Jan;20(1):61-65. doi: 10.1007/s10689-020-00192-3. Epub 2020 Jun 6.

Abstract

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.

Keywords: Genetic counseling; Germline variants; Lymphoma; Precision medicine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Ataxia Telangiectasia Mutated Proteins / genetics
  • Checkpoint Kinase 2 / genetics
  • Exome Sequencing
  • Fanconi Anemia Complementation Group N Protein / genetics
  • Female
  • Genes, Wilms Tumor
  • Genes, p53
  • Genetic Counseling
  • Germ-Line Mutation*
  • Humans
  • Lymphoma / genetics*
  • Lymphoma / mortality
  • Male
  • Middle Aged
  • Receptors, Colony-Stimulating Factor / genetics
  • Retrospective Studies

Substances

  • CSF3R protein, human
  • Fanconi Anemia Complementation Group N Protein
  • PALB2 protein, human
  • Receptors, Colony-Stimulating Factor
  • Checkpoint Kinase 2
  • ATR protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • CHEK2 protein, human