Case Study – Hospitale Universitario Virgen de las Nieves and Clínico San Cecilio

The Genetics Laboratories at the Hospitale Universitario Virgen de las Nieves and Clínico San Cecilio in Granada, Spain are affiliated with the Andalusian Health Service (Servicio Andaluz de Salud) and act as reference laboratories for the Andalusian Region, primarily investigating inherited diseases and assessing hereditary cancers. The laboratories receive and analyze hereditary cancer samples from a 1.5-million-person reference population across Granada and Huelva, assessing approximately 1000 samples per year.

Clinical research case

A 60-year-old patient was diagnosed with stage IIIC serous ovarian carcinoma and treated with chemotherapy and surgery. When aged 63, a sample was taken from the patient for genetic testing to evaluate suitability for treatment with a new PARP inhibitor. The patient’s family history included a father who died of prostate cancer at age 77, a cousin who died of lung cancer at age 45, an uncle with larynx cancer, three healthy brothers, and a healthy daughter.

Approach

The CE IVD-marked SOPHiA DDM™️ Dx Hereditary Cancer Solution v1.1 (HCS v1.1) was utilized to assess the sample.

Results

The application detected an Alu insertion in BRCA2 with 50% variant frequency: NM_000059(BRCA2):c.2197_2198ins157 (p.Val733Glyfs*22). Validation of the result with Sanger sequencing yielded confounding results – a low proportion of alignments were detected, as if it was a somatic mutation (mosaicism). These findings had both clinical and hereditary implications. Ultimately, they guided the decision that the patient was eligible to start treatment with the PARP inhibitor olaparib. The germline mutation also supported their decision to carry out genetic counselling and cascade testing of the patient’s daughter using HCS v1.1.

“The SOPHiA DDM™️ Platform enables us to quickly and confidently assess ~1000 hereditary cancer samples per year. For example, through the SOPHiA DDM™️ Dx Hereditary Cancer Solution powered by the SOPHiA DDM™️ Platform, we accurately identified a complex pathogenic Alu insertion in BRCA2 that was not clearly detected by Sanger sequencing”, says Dr. Antonio Poyatos, Hospitale Universitario Virgen de las Nieves and Clínico San Cecilio, Granada, Spain