Comprehensive Hereditary Cancer Panel
Test code: ON1001
The Blueprint Genetics Comprehensive Hereditary Cancer Panel analyzes 117 genes associated with inherited suscebtibility to cancer.
This Panel covers genes associated with a broad spectrum of hereditary cancer syndromes, conferring susceptibility to hematological and/or solid tumors. The Comprehensive Hereditary 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 covers all genes included in individual Blueprint Genetics Hereditary Cancer subpanels.
About Hereditary Cancers
Hereditary cancer syndromes account for approximately 5-10% of all cancer. These cancers originate from gastrointestinal tract, endocrine and neuroendocrine systems or from different organs like lung, kidneys, liver, pancreas, skin, and eyes. Hereditary cancer is suspected when there are multiple relatives on the same side of the family with the same or related forms of cancer, cancer at an early age or multiple cancers in an individual. The most common inherited cancer syndromes are hereditary breast and ovarian cancer syndrome, Lynch syndrome (also known as hereditary non-polyposis colorectal cancer), Li-Fraumeni syndrome, Cowden syndrome, familial adenomatous polyposis, Von-Hippel Lindau syndrome, and multiple endocrine neoplasia type 1 and type 2. Most of the hereditary cancer syndromes are inherited in an autosomal dominant manner and penetrance is high. Genetic testing is the most effective way to identify individuals with genetic predisposition of developing cancer. Accurate genetic diagnosis enables personal cancer risk assessment and inherited genetic defect can be taken into account when planning the treatment or moreover the follow-up of both unaffected and affected persons. In most of the cases, cancer mortality can be significantly reduced in high-risk individuals by regular surveillance and preventive strategies.
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: http://blueprintgenetics.com/faqs/#prenatal
|AIP||Pituitary adenoma, familial isolated||AD||54||106|
|APC||Gardner syndrome, Desmoid disease, hereditary, Familial adenomatous polyposis||AD||294||1780|
|ATM||Breast cancer, Ataxia-Telangiectasia||AD/AR||455||853|
|AXIN2||Oligodontia-colorectal cancer syndrome||AD||6||15|
|BAP1||Tumor predisposition syndrome||AD||13||73|
|BMPR1A*||Polyposis, juvenile intestinal||AD||38||108|
|BRCA1*||Pancreatic cancer, Breast-ovarian cancer, familial||AD||2207||2054|
|BRCA2||Fanconi anemia, Medulloblastoma, Glioma susceptibility, Pancreatic cancer, Wilms tumor, Breast-ovarian cancer, familial||AD/AR||2514||1791|
|BRIP1||Fanconi anemia, Breast cancer||AD/AR||87||87|
|BUB1B||Mosaic variegated aneuploidy syndrome, Premature chromatid separation trait||AD/AR||12||22|
|CDC73||Carcinoma, parathyroid, Hyperparathyroidism, Hyperparathyroidism-jaw tumor syndrome||AD||23||86|
|CDK4||Melanoma, cutaneous malignant||AD||2||11|
|CDKN1B||Multiple endocrine neoplasia||AD||9||23|
|CDKN1C||Beckwith-Wiedemann syndrome, IMAGE syndrome||AD||25||79|
|CDKN2A||Melanoma, familial, Melanoma-pancreatic cancer syndrome||AD||37||217|
|CEBPA||Acute myeloid leukemia, familial||AD||12||9|
|CEP57||Mosaic variegated aneuploidy syndrome||AR||4||3|
|CYLD||Spiegler-Brooke syndrome, Trichoepithelioma, multiple, Cylindromatosis||AD||34||103|
|DKC1||Hoyeraal-Hreidarsson syndrome, Dyskeratosis congenita||XL||45||69|
|EGFR||Lung cancer, familial, susceptibilty to, Inflammatory skin and bowel disease, neonatal, Acute myeloid leukemia, familial||AD/AR||18||19|
|EPCAM||Diarrhea 5, with tufting enteropathy, congenital, Colorectal cancer, hereditary nonpolyposis||AD/AR||15||63|
|ERCC2||Xeroderma pigmentosum, Trichothiodystrophy, photosensitive||AR||18||90|
|ERCC3||Xeroderma pigmentosum, Trichothiodystrophy, photosensitive||AR||9||16|
|ERCC4||Fanconi anemia, Xeroderma pigmentosum||AR||11||37|
|ERCC5||Xeroderma pigmentosum, Xeroderma pigmentosum/Cockayne syndrome||AR||17||51|
|EXT1||Multiple cartilagenious exostoses 1||AD||28||479|
|EXT2||Multiple cartilagenious exostoses 2||AD||20||230|
|FH||Hereditary leiomyomatosis and renal cell cancer||AD/AR||89||161|
|FLCN||Birt-Hogg-Dube syndrome, Pneumothorax, primary spontaneous||AD||85||165|
|GATA2||Myelodysplastic syndrome, Chronic neutropenia associated with monocytopenia, evolving to myelodysplasia and acute myeloid leukemia, Acute myeloid leukemia, Emberger syndrome, Immunodeficiency||AD||19||76|
|GREM1||Hereditary mixed polyposis syndrome||AD/AR||8|
|HNF1A||Maturity onset diabetes of the young, Renal cell carcinoma, nonpapillary clear cell, Liver adenomatosis||AD||47||505|
|HOXB13||Familial prostate cancer||AD/AR||6|
|HRAS||Costello syndrome, Congenital myopathy with excess of muscle spindles||AD||30||26|
|KIT||Gastrointestinal stromal tumor||AD||27||111|
|KRAS*||Noonan syndrome, Cardiofaciocutaneous syndrome||AD||46||38|
|MEN1||Hyperparathyroidism, familial primary, Multiple endocrine neoplasia||AD||124||699|
|MET||Deafness, Renal cell carcinoma, papillary||AD/AR||13||23|
|MITF||Renal cell carcinoma with or without malignant melanoma, Tietz albinism-deafness syndrome, Waardenburg syndrome, Melanoma, cutaneous malignant||AD||15||50|
|MLH1||Muir-Torre syndrome, Endometrial cancer, Mismatch repair cancer syndrome, Colorectal cancer, hereditary nonpolyposis||AD/AR||670||1084|
|MLH3||Colorectal cancer, hereditary nonpolyposis, Endometrial carcinoma||AD||4||25|
|MSH2||Muir-Torre syndrome, Endometrial cancer, Colorectal cancer, hereditary nonpolyposis,, Mismatch repair cancer syndrome||AD/AR||646||1089|
|MSH6||Endometrial cancer, Mismatch repair cancer syndrome, Colorectal cancer, hereditary nonpolyposis||AD/AR||308||426|
|MUTYH||Familial adenomatous polyposis,, Colorectal adenomatous polyposis, with pilomatricomas||AR||69||129|
|NBN||Breast cancer, Nijmegen breakage syndrome||AD/AR||57||62|
|NF1*||Watson syndrome, Neurofibromatosis, Neurofibromatosis-Noonan syndrome||AD||261||2607|
|NSD1||Sotos syndrome, Weaver syndrome, Beckwith-Wiedemann syndrome||AD||212||461|
|PALB2||Fanconi anemia, Pancreatic cancer, Breast cancer||AD/AR||237||223|
|PHOX2B||Central hypoventilation syndrome, congenital, Neuroblastoma, susceptiblity to, Neuroblastoma with Hirschsprung disease||AD||5||70|
|PMS1||Hereditary nonpolyposis colon cancer||AD/AR||1||11|
|PMS2*||Mismatch repair cancer syndrome, Colorectal cancer, hereditary nonpolyposis||AD/AR||151||266|
|POLE||Colorectal cancer, Facial dysmorphism, immunodeficiency, livedo, and short stature syndrome (FILS syndrome)||AD/AR||1||23|
|PPM1D||Hereditary breast cancer||AD||49|
|PRF1||Lymphoma, non-Hodgkin, Aplastic anemia, adult-onset, Hemophagocytic lymphohistiocytosis||AR||15||165|
|PRKAR1A||Myxoma, intracardiac, Acrodysostosis, Pigmented nodular adrenocortical disease, Carney complex||AD||50||173|
|PTCH1||Basal cell nevus syndrome||AD||46||348|
|PTEN*||Bannayan-Riley-Ruvalcaba syndrome, Lhermitte-Duclos syndrome, Cowden syndrome||AD||192||564|
|PTPN11||LEOPARD syndrome, Noonan syndrome, Metachondromatosis||AD||122||129|
|RAD51C||Fanconi anemia, Breast-ovarian cancer, familial||AD/AR||49||86|
|RAD51D||Ovarian cancer, familial||AD||25||50|
|RECQL4||Baller-Gerold syndrome, RAPADILINO syndrome, Rothmund-Thomson syndrome||AR||34||92|
|RET||Hirschsprung disease, Central hypoventilation syndrome, congenital, Pheochromocytoma, Medullary thyroid carcinoma, Multiple endocrine neoplasia||AD/AR||80||405|
|RHBDF2||Tylosis with esophageal cancer||AD||2||3|
|RUNX1||Platelet disorder, familial, with associated myeloid malignancy||AD||13||74|
|SBDS*||Aplastic anemia, Shwachman-Diamond syndrome, Severe spondylometaphyseal dysplasia||AD/AR||12||88|
|SDHA*||Leigh syndrome/Mitochondrial respiratory chain complex II deficiency, Gastrointestinal stromal tumor, Paragangliomas, Dilated cardiomyopathy (DCM)||AD/AR||23||39|
|SDHB||Paraganglioma and gastric stromal sarcoma, Pheochromocytoma, Gastrointestinal stromal tumor, Paragangliomas, Cowden-like syndrome||AD||72||249|
|SDHC||Paraganglioma and gastric stromal sarcoma, Gastrointestinal stromal tumor, Paragangliomas||AD||14||53|
|SDHD||Paraganglioma and gastric stromal sarcoma, Pheochromocytoma, Paragangliomas, Carcinoid tumors, intestinal, Cowden syndrome||AD||42||158|
|SMAD4||Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Polyposis, juvenile intestinal, Myhre dysplasia, Hereditary hemorrhagic telangiectasia||AD||119||128|
|SMARCB1||Schwannomatosis, Rhabdoid tumor predisposition syndrome||AD||17||115|
|SUFU||Medulloblastoma, Basal cell nevus syndrome||AD||7||27|
|TERC||Aplastic anemia, Pulmonary fibrosis and/or bone marrow failure, telomere-related, Dyskeratosis congenita||AD||36||60|
|TERT||Aplastic anemia, Pulmonary fibrosis and/or bone marrow failure, telomere-related, Dyskeratosis congenita||AD/AR||39||133|
|TINF2||Revesz syndrome, Dyskeratosis congenita||AD||20||33|
|TP53||Colorectal cancer, Li-Fraumeni syndrome, Ependymoma, intracranial, Choroid plexus papilloma, Breast cancer, familial, Adrenocortical carcinoma, Osteogenic sarcoma, Hepatoblastoma, Non-Hodgkin lymphoma||AD||148||391|
|TSC1||Lymphangioleiomyomatosis, Tuberous sclerosis||AD||61||306|
|TSC2||Lymphangioleiomyomatosis, Tuberous sclerosis||AD||141||977|
|VHL||Erythrocytosis, familial, Pheochromocytoma||AD/AR||143||573|
|WT1||Denys-Drash syndrome, Frasier syndrome, Wilms tumor||AD||23||165|
|XRCC2||Hereditary breast cancer||AD/AR||3||13|
*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.
|Gene||Genomic location HG19||HGVS||RefSeq||RS-number||Comment||Reference|
Blueprint Genetics offers a Comprehensive Hereditary Cancer Panel that covers classical genes associated with Beckwith-Wiedemann syndrome, Bloom syndrome, familial adenomatous polyposis, Gorlin syndrome, hereditary breast and ovarian cancer syndrome, hereditary cancer, hereditary nonpolyposis colon cancer, hereditary pheochromocytoma-paraganglioma, hereditary retinoblastoma, juvenile polyposis syndrome, Li-Fraumeni syndrome, medulloblastoma predisposition, multiple endocrine neoplasia, nephroblastoma, neurofibromatosis type 1, neurofibromatosis type 2, Peutz-Jeghers syndrome, pleuropulmonary blastoma family tumor susceptibility syndrome, Rothmund-Thomson syndrome, Simpson-Golabi-Behmel syndrome, tuberous sclerosis complex, Von Hippel-Lindau disease and Werner syndrome. 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.
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. Average sensitivity and specificity in Blueprint NGS Panels is 99.3% and 99.9% for detecting SNPs. Sensitivity to for indels vary depending on the size of the alteration: 1-10bps (96.0%), 11-20 bps (88.4%) and 21-30 bps (66.7%). The longest detected indel was 46 bps by sequence analysis. Detection limit for Del/Dup (CNV) analysis varies through the genome depending on exon size, sequencing coverage and sequence content. The sensitivity is 71.5% for single exon deletions and duplications and 99% for three exons’ deletions and duplications. We have validated the assays for different starting materials including EDTA-blood, isolated DNA (no FFPE) and saliva that all provide high-quality results. 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.
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.
Choose an analysis method
ICD & CPT codes
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.