Hereditary Gastrointestinal Cancer Panel
Test code: ON1601
The Blueprint Genetics Hereditary Gastrointestinal Cancer Panel analyzes 38 genes associated with inherited susceptibility to gastrointestinal cancer.
The panel covers genes associated with hereditary colorectal cancer syndromes, familial pancreatic cancer, hereditary diffuse gastric cancer and gastrointestinal stromal tumors. Also other syndromes associated with increased risk of gastrointestinal cancer are covered. The Hereditary Gastrointestinal Cancer Panel is suited for detecting heritable germline mutations and may not be used for the detection of somatic mutations in tumor tissue. This comprehensive Panel includes Hereditary Colorectal Cancer and Hereditary Pancreatic Cancer Panels. All genes in this Panel are included in the Comprehensive Hereditary Cancer Panel.
About Hereditary Gastrointestinal Cancer
Gastrointestinal cancers refers to malignant tumors arising from the gastrointestinal tract and accessory organs of digestion including the esophagus, stomach, pancreas, small intestine, large intestine, and rectum. Hereditary diffuse gastric cancer is caused by germline mutations in CDH1. The average age of onset is 38 years and the estimated cumulative risk of gastric cancer by age of 80 years is 80% for both men and women. Women also have a 39%-52% risk for lobular breast cancer. Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the human gastrointestinal tract. Germline mutations in KIT have been implicated in inherited susceptibility to GISTs (PMID: 16143141). Familial GIST is characterized by autosomal dominant inheritance and high penetrance. GIST rarely occurs in association with other syndromes such as neurofibromatosis type 1 , caused by germline mutations in NF1. Carney-Stratakis syndrome is characterized by paraganglioma and gastric stromal sarcoma and is caused by germline mutations in SDHB, SDHC, and SDHD (PMID: 17667967). Germline mutations in RHBDF2 have been associated with tylosis esophageal cancer that is an autosomal dominant syndrome characterized by palmoplantar keratoderma, oral precursor lesions, and a high lifetime risk of esophageal cancer (PMID: 22265016). Hereditary colorectal cancer syndromes and familial pancreatic cancer are described in the subpanels for these conditions.
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.
|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|
|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|
|BUB1B||Mosaic variegated aneuploidy syndrome, Premature chromatid separation trait||AD/AR||12||22|
|CDKN2A||Melanoma, familial, Melanoma-pancreatic cancer syndrome||AD||37||217|
|EPCAM||Diarrhea 5, with tufting enteropathy, congenital, Colorectal cancer, hereditary nonpolyposis||AD/AR||15||63|
|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|
|KIT||Gastrointestinal stromal tumor||AD||27||111|
|MEN1||Hyperparathyroidism, familial primary, Multiple endocrine neoplasia||AD||124||699|
|MLH1||Muir-Torre syndrome, Endometrial cancer, Mismatch repair cancer syndrome, Colorectal cancer, hereditary nonpolyposis||AD/AR||670||1084|
|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|
|NF1*||Watson syndrome, Neurofibromatosis, Neurofibromatosis-Noonan syndrome||AD||261||2607|
|PALB2||Fanconi anemia, Pancreatic cancer, Breast cancer||AD/AR||237||223|
|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|
|PTEN*||Bannayan-Riley-Ruvalcaba syndrome, Lhermitte-Duclos syndrome, Cowden syndrome||AD||192||564|
|RHBDF2||Tylosis with esophageal cancer||AD||2||3|
|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|
|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|
- * 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 gastrointestinal cancer panel that covers classical genes associated with APC-related attenuated familial adenomatous polyposis, ataxia telangiectasia, Carney-Stratakis syndrome, Cowden syndrome, familial adenomatous polyposis, familial pancreatic cancer, gastrointestinal cancer, gastrointestinal stromal tumor, generalized juvenile polyposis/juvenile polyposis coli, hereditary breast and ovarian cancer syndrome, hereditary diffuse gastric cancer, Li-Fraumeni syndrome, lynch syndrome, MUTYH-related attenuated familial adenomatous polyposis, palmoplantar keratoderma-esophageal carcinoma syndrome, Peutz-Jeghers syndrome and Von Hippel-Lindau disease. 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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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.