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Updated: Jul 1, 2025
Microarray-based Identification of Individual HERV Loci Expression: Application to Biomarker Discovery in Prostate Cancer
Published on: November 2, 2013
Mainstream Model of Genetic Testing for Prostate Cancer at a Large Tertiary Cancer Centre
Xin Wang1, Larissa Waldman2, Yael Silberman3
1Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Department of Medical Oncology, Sunnybrook Odette Cancer Centre, Toronto, Ontario, Canada.
Background:
An estimated 20% to 30% of men with advanced prostate cancer carry a mutation in DNA damage repair genes, of which half are estimated to be germline. Eligibility criteria for germline genetic testing expanded significantly for Ontario patients in May 2021 and many centers adopted a "mainstream" model, defined as oncologist-initiated genetic testing.
Methods:
We conducted a retrospective chart review to report on the first-year mainstream experience of a large tertiary oncologic center, the Sunnybrook Odette Cancer Centre. All patients who underwent mainstream at the discretion of their treating physician were included. A subset underwent somatic profiling as part of clinical trial screening. Descriptive statistics were used to report baseline clinicopathologic characteristics and treatments received.
Results:
Between May 1, 2021, and May 30, 2022, 174 patients with prostate cancer underwent mainstream germline genetic testing with a 19-gene panel. Median age was 75 (IQR 68-80), and 82% of patients were diagnosed with either de novo metastatic or high-risk localized prostate adenocarcinoma. Fourteen patients (8%; 95% CI 4%-12%) were found to have a deleterious germline mutation, including pathogenic or likely pathogenic variants in BRCA1/2, ATM, CHEK2, PMS2, RAD51C, HOXB13, and BRIP1. Forty-nine patients (28%; 95% CI 21%-35%) were found to have a variant of uncertain significance. Thirty-four patients also had next-generation sequencing (NGS) of their somatic tissue. Among this subset, 8 of 34 (23%) had an alteration in homologous recombination repair (HRR) genes. Of the 14 patients with a germline mutation, none had a prior personal history of malignancy and 6 (43%) did not have any first- or second-degree relatives with history of prostate, pancreatic, breast, or ovarian cancer.
Conclusion:
We report on the real-world characteristics of prostate cancer patients who underwent mainstream germline genetic testing. Personal history and family history of cancer cannot reliably stratify patients for the presence of pathogenic germline variants.
Insights
Mainstream germline genetic testing in advanced prostate cancer identified deleterious mutations in 8% of patients. Family and personal cancer history were not reliable indicators for these mutations, highlighting the need for broader testing.
Area of Science:
- Oncology
- Genetics
- Cancer Research
Background:
- Approximately 20-30% of advanced prostate cancer cases involve DNA damage repair gene mutations, with half potentially being germline.
- Ontario expanded germline genetic testing eligibility in May 2021, promoting a mainstream, oncologist-initiated model.
Purpose of the Study:
- To evaluate the initial year of mainstream germline genetic testing implementation at a major cancer center.
- To analyze the characteristics of prostate cancer patients undergoing this testing and identify germline mutations.
Main Methods:
- A retrospective chart review was conducted at the Sunnybrook Odette Cancer Centre.
- 174 prostate cancer patients undergoing mainstream germline genetic testing (19-gene panel) between May 2021 and May 2022 were included.
- Somatic profiling via next-generation sequencing (NGS) was performed on a subset of patients.
Main Results:
- 8% of patients (14/174) harbored deleterious germline mutations in genes including BRCA1/2, ATM, and CHEK2.
- 28% of patients had variants of uncertain significance.
- Among patients with germline mutations, none had a personal cancer history, and 43% lacked relevant family cancer history.
Conclusions:
- Mainstream germline genetic testing in prostate cancer patients reveals a significant rate of pathogenic germline variants.
- Personal and family history are insufficient to identify all patients with these mutations, underscoring the value of broad genetic screening.
