Article Text

MG-131 Incidental germline findings in tumour molecular profiling by next generation sequencing
  1. Tracy L Stockley1,2,3,
  2. Mariam Thomasa3,
  3. Djamel Harbia3,
  4. Mahadeo Sukhai1,3,
  5. Tong Zhang1,3,
  6. Trevor Pugha3,4,
  7. Lillian Siu3,5,
  8. Phil Bedard3,5,
  9. Suzanne Kamel Reid1,2,3
  1. 1Laboratory Medicine Program, Molecular Diagnostics, Department of Pathology, University Health Network, Toronto, ON, Canada
  2. 2Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
  3. 3Cancer Genomics Program, Princess Margaret Cancer Centre, Toronto, ON, Canada
  4. 4Department of Medical Biophyics, University of Toronto, Toronto, ON, Canada
  5. 5Division of Medical Oncology, Princess Margaret Cancer Centre, Toronto, ON, Canada


Objectives Molecular profiling of solid tumours using Next Generation Sequencing (NGS) aims to detect tumour-specific somatic mutations for targeted drug treatments. Parallel testing of tumour and blood samples can enable identification and verification of of tumour-specific somatic mutations. However testing blood may also reveal incidental germline variants in cancer predisposition genes. The objective of this study was to determine type and frequency of clinically relevant incidental germline variants from molecular profiling of paired tumour/blood samples.

Design/methods NGS molecular profiling data of tumour/blood pairs from 467 patients (934 samples) with metastatic solid tumours enrolled in the Princess Margaret IMPACT clinical trial were reviewed. NGS testing used Illumina TruSeq Cancer Amplicon Panel (TSCAP) on the MiSeq. The TSCAP targets regions of 48 genes including 8 genes on the ACMG germline incidental list (APC, PTEN, MLH1, RET, RB1, STK11, TP53, VHL).

Results Data review revealed 2 previously reported pathogenic cancer predisposition mutations: TP53 c.817C >T in a breast cancer patient, and RET c.1900T >A in a thyroid cancer patient. Three other patients had acquired mutations of JAK2 or TP53 in blood, confirmed by serial testing that likely represented secondary changes related to previous cancer treatments. In addition 93 germline variants of uncertain significance were identified; 9/93 were recurrent and may represent benign germline changes.

Conclusions Solid tumour NGS molecular profiling using paired tumour/blood samples can incidentally identify pathogenic germline mutations in cancer predisposition genes. Appropriate consent and genetic counselling support is crucial for NGS tumour molecular profiling using blood/tumour pairs.

Statistics from

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.