Early-onset breast cancer in a woman with a germline mobile element insertion resulting in BRCA2 disruption: a case report

Natalie Deuitch; Shao-Tzu Li; Eliza Courtney; Tarryn Shaw; Rebecca Dent; Veronique Tan; Lauren Yackowski; Rebecca Torene; Windy Berkofsky-Fessler; Joanne Ngeow

doi:10.1038/s41439-020-00111-z

Early-onset breast cancer in a woman with a germline mobile element insertion resulting in BRCA2 disruption: a case report

Hum Genome Var. 2020 Aug 25:7:24. doi: 10.1038/s41439-020-00111-z. eCollection 2020.

Authors

Natalie Deuitch^{1

2}, Shao-Tzu Li¹, Eliza Courtney¹, Tarryn Shaw¹, Rebecca Dent³, Veronique Tan⁴, Lauren Yackowski⁵, Rebecca Torene⁵, Windy Berkofsky-Fessler⁵, Joanne Ngeow^{1

6}

Affiliations

¹ Cancer Genetics Service, Division of Medical Oncology, National Cancer Centre, Singapore, Singapore.
² Department of Genetics, Stanford University School of Medicine, Stanford, CA USA.
³ Division of Medical Oncology, National Cancer Centre, Singapore, Singapore.
⁴ Division of Breast Surgical Oncology, National Cancer Centre, Singapore, Singapore.
⁵ Hereditary Cancer Program, GeneDx, Gaithersburg, MD USA.
⁶ Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.

Abstract

Mobile element insertions (MEIs) contribute to genomic diversity, but they can be responsible for human disease in some cases. Initial clinical testing (BRCA1, BRCA2 and PALB2) in a 40-year-old female with unilateral breast cancer did not detect any pathogenic variants. Subsequent reanalysis for MEIs detected a novel likely pathogenic insertion of the retrotransposon element (RE) c.7894_7895insSVA in BRCA2. This case highlights the importance of bioinformatic pipeline optimization for the detection of MEIs in genes associated with hereditary cancer, as early detection can significantly impact clinical management.

Keywords: Cancer genomics; Next-generation sequencing.