Tumor genome analysis includes germline genome: are we ready for surprises?

Int J Cancer. 2015 Apr 1;136(7):1559-67. doi: 10.1002/ijc.29128. Epub 2014 Aug 14.


We sought to describe the spectrum of potential and confirmed germline genomic events incidentally identified during routine medium-throughput somatic tumor DNA sequencing, and to provide a framework for pre- and post-test consent and counseling for patients and families. Targeted tumor-only next-generation sequencing (NGS) had been used to evaluate for possible druggable genomic events obtained from consecutive new patients with metastatic gastroesophageal, hepatobiliary or colorectal cancer seen at the University of Chicago. A panel of medical oncologists, cancer geneticists and genetic counselors retrospectively grouped these patients (N = 111) based on probability of possessing a potentially inherited mutation in a cancer susceptibility gene, both prior to and after incorporating tumor-only NGS results. High-risk patients (determined from NGS results) were contacted and counseled in person by a genetic counselor (N = 21). When possible and indicated, germline genetic testing was offered. Of 8 evaluable high-risk patients, 7 underwent germline testing. Three (37.5%) had confirmed actionable germline mutations (all in the BRCA2 gene). NGS offers promise, but poses significant challenges for oncologists who are ill prepared to handle incidental findings that have clinical implications for at risk family members. In this relatively small cohort of patients undergoing tumor genomic testing for gastrointestinal malignancies, we incidentally identified 3 BRCA2 mutations carriers. This report underscores the need for oncologists to develop a framework for pre- and post-test communication of risks to patients undergoing routine tumor-only sequencing.

Keywords: genetic counseling; germline; next generation sequencing; somatic.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Chromosome Aberrations
  • Early Detection of Cancer
  • Family
  • Female
  • Genetic Counseling
  • Genetic Testing
  • Genomics*
  • Germ Cells / metabolism*
  • Germ-Line Mutation
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Middle Aged
  • Neoplasms / diagnosis
  • Neoplasms / genetics*
  • Retrospective Studies