Somatic mutation profiling in BRCA-negative breast and ovarian cancer patients by multigene panel sequencing
Ava Kwong1,2,3, Isabella Wy Cheuk1, Vivian Yvonne Shin1
1Department of Surgery, The University of Hong Kong and The University of Hong Kong-Shenzhen Hospital Hong Kong SAR.
Abstract:
Targeted therapeutic agents such as poly (ADP-ribose) polymerases (PARP) inhibitors have emerged in treating cancers associated with germline BRCA mutations. Recently studies demonstrated the effectiveness of PARP inhibitors in treating patients with somatic BRCA mutations. Somatic mutations in 122 Chinese breast or ovarian cancer patients without BRCA, PTEN and TP53 mutations were screened using multigene sequencing panel. The five most frequent pathogenic or likely pathogenic mutated genes identified in breast cancer patients were PIK3CA (28.6%), TP53 (16.9%), MAP3K1 (14.3%), GATA3 (14.3%) and PTEN (5.2%). The five most frequently mutated genes identified in ovarian patients were TP53 (52.9%), KRAS (23.5%) and PIK3CA (11.8%), BRCA1 (5.9%) and RB1 (5.9%). Somatic PIK3CA and TP53 mutations were common events in both germline BRCA-negative breast and ovarian cancer patients. In contrast, somatic screening of BRCA mutations in BRCA-negative breast cancer patients has limited value. The results highlight the benefit of somatic testing to guide future research directions on other targeted therapies for breast and ovarian malignancies.
Insights
Poly (ADP-ribose) polymerases (PARP) inhibitors show promise for cancers with somatic BRCA mutations. Somatic PIK3CA and TP53 mutations are common in BRCA-negative breast and ovarian cancers, guiding targeted therapy research.
Area of Science:
- Oncology
- Genetics
- Cancer Research
Background:
- Poly (ADP-ribose) polymerases (PARP) inhibitors are effective for cancers with germline BRCA mutations.
- Emerging evidence suggests PARP inhibitors are also effective for cancers with somatic BRCA mutations.
Purpose of the Study:
- To screen for somatic mutations in Chinese breast and ovarian cancer patients without germline BRCA, PTEN, and TP53 mutations.
- To identify frequently mutated genes in these patient cohorts to guide future targeted therapy research.
Main Methods:
- Multigene sequencing panel used to screen 122 Chinese breast or ovarian cancer patients.
- Focus on patients without germline BRCA, PTEN, and TP53 mutations.
Main Results:
- In breast cancer patients, the most frequent mutations were PIK3CA (28.6%), TP53 (16.9%), MAP3K1 (14.3%), GATA3 (14.3%), and PTEN (5.2%).
- In ovarian cancer patients, the most frequent mutations were TP53 (52.9%), KRAS (23.5%), PIK3CA (11.8%), BRCA1 (5.9%), and RB1 (5.9%).
- Somatic PIK3CA and TP53 mutations were common in germline BRCA-negative breast and ovarian cancer patients. Somatic BRCA mutation screening had limited value in BRCA-negative breast cancer patients.
Conclusions:
- Somatic PIK3CA and TP53 mutations are prevalent in germline BRCA-negative breast and ovarian cancers.
- Somatic mutation testing is valuable for guiding targeted therapy research in breast and ovarian malignancies.
- Somatic BRCA mutation screening is less valuable in BRCA-negative breast cancer patients.
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