Germline potential should not be overlooked for cancer variants identified in tumour-only somatic mutation testing

Pathology. 2024 Jun;56(4):468-472. doi: 10.1016/j.pathol.2024.03.001. Epub 2024 Mar 29.


DNA sequencing of tumour tissue has become the standard care for many solid cancers because of the option to detect somatic variants that have significant therapeutic, diagnostic and prognostic implications. Variants found within the tumour may be either somatic or germline in origin. Somatic cancer gene panels are developed to detect acquired (somatic) variants that are relevant for therapeutic or molecular characterisation of the tumour, expanding gene panels now include genes which may also inform patient management such as cancer predisposition syndromes (CPS) genes. Identifying germline cancer predisposition variants can alter cancer management, the risk of developing new primary cancers and risk for cancer in at-risk family members. This paper discusses the clinical, technical and ethical challenges related to identifying and reporting potential germline pathogenic variants that are detected on tumour sequencing. It also highlights the existence of the eviQ national guidelines for CPS with advice on germline confirmation of somatic findings to pathology laboratories in Australia.

Keywords: Somatic mutation testing; germline pathogenic variants; somatic variants; tumour-only sequencing.

Publication types

  • Review

MeSH terms

  • Australia
  • DNA Mutational Analysis
  • Genetic Predisposition to Disease*
  • Genetic Testing
  • Germ-Line Mutation*
  • Humans
  • Neoplasms* / diagnosis
  • Neoplasms* / genetics
  • Neoplasms* / pathology