Test Code: 9791

High Risk Breast Cancer: Sequencing and Deletion/Duplication Panel
Test Code: 9791
Turnaround time: 3 weeks


Most cases of breast cancer are sporadic with no family history of the cancer; but, 5-10% of cases are understood to be due to a hereditary predisposition. Nearly 1 in 8 women (12%) will develop breast cancer in their lifetime (SEER). The clinical features suggestive of a hereditary cancer predisposition involve: diagnosis at a young age (< 50), multiple primary cancers in a single individual, diagnosis of a cancer type that is not common in the general population (such as male breast cancer, ovarian cancer, or pancreatic cancer), and several relatives affected with related cancers over multiple generations.

CEN4GEN’s High Risk Breast Cancer Panel includes genes involved in hereditary cancer predisposition syndromes, including hereditary breast and ovarian cancer syndrome (BRCA1 and BRCA2), hereditary diffuse gastric cancer syndrome (CDH1), Li-Fraumeni syndrome (TP53 and PTEN), hamartoma tumor syndrome (PTEN), and Peutz-Jeghers syndrome (STK11).

It is estimated that 20-25% of familial breast cancer risk can be ascribed to mutations in the BRCA1 or BRCA2 genes (van der Groep 2011). The contribution of mutations in the CDH1, PTEN, STK11, and TP53 genes to familial breast cancer risk is considerably lower than the contribution of BRCA1 and BRCA2 mutations.

Genes not included in the deletion/duplication analysis are: CDH1 and PALB2.


  • Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute. SEER Cancer Statistics Review, 1975-2009: Lifetime Risk Tables (URL: http://surveillance.cancer.gov/devcan).
  • Van der Groep P, van der Wall E, and van Diest PJ. Pathology of hereditary breast cancer. Cell Oncol (Dordrecht). 2011 Apr;34(2):71-88. (PMID: 21336636).


This test is indicated for:

  • Confirmation of a clinical diagnosis of high risk breast cancer.


Next Generation Sequencing: In-solution hybridization of all coding exons is performed on the patient’s genomic DNA. Although some deep intronic regions may also be analyzed, this assay is not mean to interrogate most promoter regions, deep intronic regions, or other regulatory elements, and does not detect single or multi-exon deletions or duplications. Direct sequencing of the captured regions is performed using next generation sequencing. The patient’s gene sequences are then compared to a standard reference sequence. Potentially causative variants and areas of low coverage are Sanger-sequenced. Sequence variations are classified as pathogenic, likely pathogenic, benign, likely benign, or variants of unknown significance. Variants of unknown significance may require further studies of the patient and/or family members.

Deletion/Duplication Analysis: DNA isolated from peripheral blood is hybridized to a gene-targeted CGH array to detect deletions and duplications. The targeted CGH array has overlapping probes that cover the entire genomic region.Please note that the following genes do not have deletion/duplication analysis included in this panel: CDH1 and PALB2.

Please note that a “backbone” of probes across the entire genome are included on the array for analytical and quality control purposes. Rarely, off- target copy number variants causative of disease may be identified that may or may not be related to the patient’s phenotype. Only known pathogenic off-target copy number variants will be reported. Off-target copy number variants of unknown clinical significance will not be reported.


Next Generation Sequencing: Clinical Sensitivity: Unknown. Mutations in the promoter region, some mutations in the introns and other regulatory element mutations cannot be detected by this analysis. Large deletions/duplications will not be detected by this analysis. Results of molecular analysis should be interpreted in the context of the patient’s clinical/biochemical phenotype.

Analytical Sensitivity: ~99%.

Deletion/Duplication Analysis: Detection is limited to duplications and deletions. The CGH array will not detect point or intronic mutations. Results of molecular analysis must be interpreted in the context of the patient’s clinical and/or biochemical phenotype.


Submit only 1 of the following specimen types

Type: Whole Blood
Specimen Requirements: In EDTA (purple top) tube: Infants (2 years): 3-5 ml
Older Children & Adults: 5-10 ml.

Specimen Collection and Shipping: Ship sample at room temperature with overnight delivery.

Type: Isolated DNA
Specimen Requirements: In microtainer: 60 μg
Isolation using the QiagenTM Puregene kit for DNA extraction is recommended.

Specimen Collection and Shipping: Refrigerate until time of shipment in 100 ng/ul of TE buffer. Ship sample at room temperature with overnight delivery.

This test is for germline mutation analysis. DNA isolated from FFPE tumor samples is not suitable for this test.


  • BRCA1/BRCA2 Gene Sequencing and Deletion/Duplication Panel
  • BRCA1/BRCA2 Gene Sequencing Panel
  • BRCA1/BRCA2 Deletion/Duplication Panel
  • Hereditary Cancer Syndrome: Sequencing Panel