Hereditary Breast and Gynecological Cancer Panel

SEQmethod-seq-icon Our Sequence Analysis is based on a proprietary targeted sequencing method OS-Seq™ and offers panels targeted for genes associated with certain phenotypes. A standard way to analyze NGS data for finding the genetic cause for Mendelian disorders. Results in 21 days. DEL/DUPmethod-dup-icon Targeted Del/Dup (CNV) analysis is used to detect bigger disease causing deletions or duplications from the disease-associated genes. Results in 21 days. PLUSmethod-plus-icon Plus Analysis combines Sequence + Del/Dup (CNV) Analysis providing increased diagnostic yield in certain clinical conditions, where the underlying genetic defect may be detectable by either of the analysis methods. Results in 21 days.

Test code: ON1801

The Blueprint Genetics Hereditary Breast and Gynecological Cancer Panel analyzes 27 genes associated with inherited susceptibility to breast and gynecological cancer.

Breast cancer is the most common cancer in women. Gynecological cancers are originating in the female reproductive organs and include cervical, ovarian, uterine, vaginal, and vulvar cancers. Breast and gynecological cancers are usually sporadic but 5-10% of the disease onset is caused by pathogenic mutations in cancer susceptibility genes. Inheritance pattern of these genetic cancer predisposition conditions is autosomal dominant. The Hereditary Breast and Gynecological Cancer Panel is suited for detecting heritable germline mutations and may not be used for the detection of somatic mutations in tumor tissue. This Panel includes the Breast Cancer High Risk Panel and is part of the Comprehensive Hereditary Cancer Panel.

About breast and gynecological cancer

The most common hereditary cancer syndromes that are associated with increased risk of breast and gynecological cancers are hereditary breast and ovarian cancer syndrome and Lynch syndrome, also known as hereditary nonpolyposis colon cancer (HNPCC). Carriers of pathogenic mutations in BRCA1 and BRCA2 have an increased risk of breast cancer and, the lifetime risk of having one of the gynecologic cancers is 39-46% and 12-20%, respectively. Lynch syndrome is caused by inherited mutations in DNA mismatch repair genes, most often MSH2 and MLH1, but mutations also occur in MSH6,PMS2, and EPCAM. There is an increased incidence of several types of cancers in HNPCC, most notably of the gynecological cancers, endometrial cancer risk is 40-60%. Several other syndromes and genetic defects have been identified to increase the risk of breast and gynecological cancers. For example, Li-Fraumeni syndrome (TP53), Cowden syndrome (PTEN) and Peutz-Jeghers syndrome (STK11) increase the likelihood of having an inherited predisposition to breast and gynecological cancer. Mutations in DNA repair genes, RAD51C, RAD51D, and BRIP1, have shown clear evidence of an association with ovarian cancer. Protein truncating variants in CHEK2 and ATM have been shown to confer moderate risk for breast cancer.

Availability

Results in 3-4 weeks. We do not offer a maternal cell contamination (MCC) test at the moment. We offer prenatal testing only for cases where the maternal cell contamination studies (MCC) are done by a local genetic laboratory. Read more.

Genes in the Hereditary Breast and Gynecological Cancer Panel and their clinical significance
GeneAssociated phenotypesInheritanceClinVarHGMD
ATMBreast cancer, Ataxia-TelangiectasiaAD/AR455853
BARD1Breast cancerAD5453
BLMBloom syndromeAR5392
BRCA1*Pancreatic cancer, Breast-ovarian cancer, familialAD22072054
BRCA2Fanconi anemia, Medulloblastoma, Glioma susceptibility, Pancreatic cancer, Wilms tumor, Breast-ovarian cancer, familialAD/AR25141791
BRIP1Fanconi anemia, Breast cancerAD/AR8787
CDH1CDH1-related cancerAD66183
CHEK2*Li-Fraumeni syndromeAD/AR93115
DICER1*DICER1 syndromeAD96109
EPCAMDiarrhea 5, with tufting enteropathy, congenital, Colorectal cancer, hereditary nonpolyposisAD/AR1563
FANCCFanconi anemiaAR3434
MLH1Muir-Torre syndrome, Endometrial cancer, Mismatch repair cancer syndrome, Colorectal cancer, hereditary nonpolyposisAD/AR6701084
MRE11AAtaxia-telangiectasia-like disorder-1AD2538
MSH2Muir-Torre syndrome, Endometrial cancer, Colorectal cancer, hereditary nonpolyposis,, Mismatch repair cancer syndromeAD/AR6461089
MSH6Endometrial cancer, Mismatch repair cancer syndrome, Colorectal cancer, hereditary nonpolyposisAD/AR308426
NBNBreast cancer, Nijmegen breakage syndromeAD/AR5762
NF1*Watson syndrome, Neurofibromatosis, Neurofibromatosis-Noonan syndromeAD2612607
PALB2Fanconi anemia, Pancreatic cancer, Breast cancerAD/AR237223
PMS2*Mismatch repair cancer syndrome, Colorectal cancer, hereditary nonpolyposisAD/AR151266
PPM1DHereditary breast cancerAD49
PTEN*Bannayan-Riley-Ruvalcaba syndrome, Lhermitte-Duclos syndrome, Cowden syndromeAD192564
RAD50Breast cancerAD7440
RAD51CFanconi anemia, Breast-ovarian cancer, familialAD/AR4986
RAD51DOvarian cancer, familialAD2550
STK11Peutz-Jeghers syndromeAD69399
TP53Colorectal cancer, Li-Fraumeni syndrome, Ependymoma, intracranial, Choroid plexus papilloma, Breast cancer, familial, Adrenocortical carcinoma, Osteogenic sarcoma, Hepatoblastoma, Non-Hodgkin lymphomaAD148391
XRCC2Hereditary breast cancerAD/AR313
  • * Some regions of the gene are duplicated in the genome leading to limited sensitivity within the regions. Thus, low-quality variants are filtered out from the duplicated regions and only high-quality variants confirmed by other methods are reported out. Read more.

Gene, refers to HGNC approved gene symbol; Inheritance to inheritance patterns such as autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL); ClinVar, refers to a number of variants in the gene classified as pathogenic or likely pathogenic in ClinVar (http://www.ncbi.nlm.nih.gov/clinvar/); HGMD, refers to a number of variants with possible disease association in the gene listed in Human Gene Mutation Database (HGMD, http://www.hgmd.cf.ac.uk/ac/). The list of associated (gene specific) phenotypes are generated from CDG (http://research.nhgri.nih.gov/CGD/) or Orphanet (http://www.orpha.net/) databases.

Blueprint Genetics offers a comprehensive hereditary breast and gynecological cancer panel that covers classical genes associated with gynecological cancer. The genes are carefully selected based on the existing scientific evidence, our experience and most current mutation databases. Candidate genes are excluded from this first-line diagnostic test. The test does not recognise balanced translocations or complex inversions, and it may not detect low-level mosaicism. The test should not be used for analysis of sequence repeats or for diagnosis of disorders caused by mutations in the mitochondrial DNA.

Please see our latest validation report showing sensitivity and specificity for SNPs and indels, sequencing depth, % of the nucleotides reached at least 15x coverage etc. If the Panel is not present in the report, data will be published when the Panel becomes available for ordering. Analytical validation is a continuous process at Blueprint Genetics. Our mission is to improve the quality of the sequencing process and each modification is followed by our standardized validation process. All the Panels available for ordering have sensitivity and specificity higher than > 0.99 to detect single nucleotide polymorphisms and a high sensitivity for indels ranging 1-19 bp. The diagnostic yield varies substantially depending on the used assay, referring healthcare professional, hospital and country. Blueprint Genetics’ Plus Analysis (Seq+Del/Dup) maximizes the chance to find molecular genetic diagnosis for your patient although Sequence Analysis or Del/Dup Analysis may be cost-effective first line test if your patient’s phenotype is suggestive for a specific mutation profile. Detection limit for Del/Dup analysis varies through the genome from one to six exon Del/Dups depending on exon size, sequencing coverage and sequence content.

The sequencing data generated in our laboratory is analyzed with our proprietary data analysis and annotation pipeline, integrating state-of-the art algorithms and industry-standard software solutions. Incorporation of rigorous quality control steps throughout the workflow of the pipeline ensures the consistency, validity and accuracy of results. The highest relevance in the reported variants is achieved through elimination of false positive findings based on variability data for thousands of publicly available human reference sequences and validation against our in-house curated mutation database as well as the most current and relevant human mutation databases. Reference databases currently used are the 1000 Genomes Project (http://www.1000genomes.org), the NHLBI GO Exome Sequencing Project (ESP; http://evs.gs.washington.edu/EVS), the Exome Aggregation Consortium (ExAC; http://exac.broadinstitute.org), ClinVar database of genotype-phenotype associations (http://www.ncbi.nlm.nih.gov/clinvar) and the Human Gene Mutation Database (http://www.hgmd.cf.ac.uk). The consequence of variants in coding and splice regions are estimated using the following in silico variant prediction tools: SIFT (http://sift.jcvi.org), Polyphen (http://genetics.bwh.harvard.edu/pph2/), and Mutation Taster (http://www.mutationtaster.org).

Through our online ordering and statement reporting system, Nucleus, the customer can access specific details of the analysis of the patient. This includes coverage and quality specifications and other relevant information on the analysis. This represents our mission to build fully transparent diagnostics where the customer gains easy access to crucial details of the analysis process.

In addition to our cutting-edge patented sequencing technology and proprietary bioinformatics pipeline, we also provide the customers with the best-informed clinical report on the market. Clinical interpretation requires fundamental clinical and genetic understanding. At Blueprint Genetics our geneticists and clinicians, who together evaluate the results from the sequence analysis pipeline in the context of phenotype information provided in the requisition form, prepare the clinical statement. Our goal is to provide clinically meaningful statements that are understandable for all medical professionals, even without training in genetics.

Variants reported in the statement are always classified using the Blueprint Genetics Variant Classification Scheme modified from the ACMG guidelines (Richards et al. 2015), which has been developed by evaluating existing literature, databases and with thousands of clinical cases analyzed in our laboratory. Variant classification forms the corner stone of clinical interpretation and following patient management decisions. Our statement also includes allele frequencies in reference populations and in silico predictions. We also provide PubMed IDs to the articles or submission numbers to public databases that have been used in the interpretation of the detected variants. In our conclusion, we summarize all the existing information and provide our rationale for the classification of the variant.

A final component of the analysis is the Sanger confirmation of the variants classified as likely pathogenic or pathogenic. This does not only bring confidence to the results obtained by our NGS solution but establishes the mutation specific test for family members. Sanger sequencing is also used occasionally with other variants reported in the statement. In the case of variant of uncertain significance (VUS) we do not recommend risk stratification based on the genetic finding. Furthermore, in the case VUS we do not recommend use of genetic information in patient management or genetic counseling. For some cases Blueprint Genetics offers a special free of charge service to investigate the role of identified VUS.

We constantly follow genetic literature adapting new relevant information and findings to our diagnostics. Relevant novel discoveries can be rapidly translated and adopted into our diagnostics without delay. These processes ensure that our diagnostic panels and clinical statements remain the most up-to-date on the market.

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ICD & CPT codes

CPT codes

SEQ81432
DEL/DUP81479

Accepted sample types

  • EDTA blood, min. 1 ml
  • Purified DNA, min. 5μg
  • Saliva (Oragene DNA OG-500 kit)

Label the sample tube with your patient’s name, date of birth and the date of sample collection.

Note that we do not accept DNA samples isolated from formalin-fixed paraffin-embedded (FFPE) tissue.

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