NGS - ACTBRCA®
2 genes (BRCA1/2)
BRCA1/2 is the most common gene mutation in hereditary breast cancer and has also been found to be associated with ovarian cancer, pancreatic cancer, prostate cancer, etc. In recent years, selection of cancer patients who would likely benefit from PARP inhibitor treatment also relies on the detection of BRCA1/2 mutations, thus emphasizing the importance of BRCA1/2 genetic testing.
BRCA1/2 Genetic Information
Individuals with deleterious or likely deleterious germline BRCA1/2 mutations are known to have an increased lifetime risk of breast, ovarian, pancreatic, and prostate cancers1. Therefore, a genetic testing for germline BRCA1/2 mutations allows the lifetime risk of hereditary cancers to be determined, so that risk mitigation actions such as active surveillance and other preventive measures can be taken timely through appropriate genetic counseling.
According to the latest NCCN guideline, genetic counseling is recommended in breast cancer patients and their families if they fulfill the following characteristics:
(1) With a known pathogenic/likely pathogenic variant in a cancer susceptibility gene
(2) Personal or family history of ovarian cancer
(3) Personal or family history of bilateral breast cancer
(4) Early-onset breast cancer at ≤45 years of age
(5) Triple negative breast cancer at ≤60 years of age
(6) At least 1 close blood relative with breast cancer at ≤50 years of age or at least 3 total diagnoses of breast cancer in a family.
(7) Family history of pancreas
(8) Family history of male breast cancer
*Consultation with a physician or a professional genetic counselor is highly recommended before, during, and/or after the test*
PARP Inhibitor Treatment
PARP inhibitors are pharmacological agents that block the activity of a family of DNA damage repair (DDR) proteins called PARPs, which are responsible for repairing single-strand breaks before DNA replication and cell division. If the single-strand breaks remain unrepaired and persist through the DNA replication process, double-strand breaks are formed as a result. PARP inhibitors cause the formation of double-strand breaks by trapping at the sites of single-strand DNA breaks.
In tumors with homologous recombination repair (HRR) deficiency (also known as HRD, which is caused by mutations in BRCA1/2 or other HRR genes), these double-strand breaks cannot be properly repaired, ultimately leading to cell death in a phenomenon called synthetic lethality whereby the combination of two individually non-lethal defects (i.e., PARP inhibition and HRD) leads to a unique vulnerability.
Clinical Experience from Ovarian Cancer: Both Germline and Somatic BRCA1/2 Mutations Play an Important Role in Cancer
The normal and tumor tissue samples of 99 patients with ovarian cancer were analyzed for BRCA1/2 mutations using next-generation genetic sequencing and Sanger gene sequencing. Pathogenic BRCA1/2 variants were found in 12 patients. It is notable in one patient that both germline BRCA1 and somatic BRCA2 mutations were found. Interestingly, all of the 12 patients with pathogenic BRCA1/2 mutations had serous carcinoma, suggesting that ovarian cancer with these BRCA gene mutations exhibit similar pathological morphology. Five of these 12 patients (~42%) had a BRCA gene mutation that was solely detectable in tumor tissue and not in normal tissue, indicative of the sporadic nature of these mutations. This study exemplifies that BRCA gene mutations, whether inherited or acquired, can play a key role in the pathogenesis of ovarian cancer.
*Abbreviations: gBRCA: germline BRCA; sBRCA: somatic BRCA.
1. Venkitaraman AR. Annu Rev Pathol 2009; 4: 461-487.
2. Ford D, et al. Lancet. 1994;343:692-695.
3. Struewing JP, et al.N Engl J Med. 1997;336:1401-1408.
4. Li X, Heyer WD. Cell Res. 2008;18:99-113.
5. Lord CJ, Ashworth A. Nat Rev Cancer. 2016;16:110-120.
6. Hartwell LH, Szankasi P, Roberts CJ, et al. Science 1997; 278: 1064-1068.
7. Venkitaraman AR, . Science 2014; 343: 1470-1475
8. Livraghi L, Garber JE. BMC Med 2015; 13:188.
9. Farmer H, McCabe N, Lord CJ, et al.Nature 2005; 434: 917-921
10. Bryant HE, Schultz N, Thomas HD, et al. Nature 2005; 434: 913-917.
1. Complete BRCA Genetic Information
A comprehensive BRCA1/2 testing which includes coding exons and splicing regions. NGS technology is used to detect multiple mutation types such as single nucleotide variants (SNVs), small insertions and deletions (InDels), as well as large genomic rearrangements (LGRs) through a proprietary algorithm (pattern application in progress).
2. Up-to-date Bioinformatic Analysis based on International Databases
Bioinformatic analysis is carried out by a team of dedicated and experienced bioinformatians with solid clinical genetics background. Information extracted from international databases such as gnomAD, 1000 Genome, ClinVar, COSMIC, as well as ACT Genomics’ self-built ethnographic database, provide relevant interpretation and useful insights on the variants identified.
3. A Clear and Detailed Medical Report
The report provides recommendations in accordance with the latest ACMG Guidelines and AMP Guidelines, as well as other relevant information such as disease risk based on the currently available clinical literature.
4. Quality Guaranteed
All tests carried out by ACT Genomics are conducted in a CAP-certified laboratory, which has also garnered the LDTS (Laboratory Developed Tests and Services) certification by the Taiwan FDA.
5. Short turnaround time: 10 working days
NGS - ACTBRCA®
2 genes (BRCA1/2)
Sensitivity - ACTBRCA®
Specificity - ACTBRCA®
Sample Types - ACTBRCA®
Sequencing Mean Depth
≥ 1000 x