- Hereditary cancer syndromes are encountered in all medical specialties. Although they account for about 5% of all malignancies, it is of special importance to identify these patients because, unlike patients with sporadic cancers, they require special, long-term care as their predisposition can cause them to develop certain tumors at a relatively early age. These cancers can arise in the lungs, kidneys, liver, pancreas, skin, eyes, heart. Most hereditary cancers are associated with a “germline mutation” that will be present in every cell of the human body. Identification of patients at risk of inherited cancer susceptibility is dependent upon the ability to characterize genes and alterations associated with increased cancer risk as well as gathering a detailed personal and family history aiding in the identification of the mode of inheritance as well as other family members at risk of suffering from this susceptibility. Most hereditary cancer syndromes follow an autosomal dominant inheritance, and the penetrance is high.
- The Igenomix Hereditary Colorectal Cancer Precision Panel provides a comprehensive analysis of the most common hereditary Colorectal Cancer syndromes using next-generation sequencing (NGS) to fully understand the spectrum of relevant colorectal cancer predisposition genes.
The Igenomix Hereditary Colorectal Cancer Panel is indicated as a screening and diagnostic test in those cases where there is:
- Family history of colorectal cancer (CRC) or suspected hereditary colorectal cancer syndrome, such as familial adenomatous polyposis (FAP) or Lynch syndrome (hereditary non-polyposis colon cancer or HNPCC).
- Family or personal history of Lynch syndrome or Lynch-like syndrome.
- History of multiple colorectal adenomas.
- Asymptomatic patient who wishes to know genetic risk for CRC.
- A personal history of getting radiation to the abdomen or pelvic area to treat prior cancer.
- Personal history of inflammatory bowel disease (Ulcerative Colitis or Crohn’s disease).
- The genetic and molecular diagnosis for an accurate clinical diagnosis of a patient with personal or family history suggestive of a hereditary cancer syndrome.
- Early initiation of treatment with a multidisciplinary team for appropriate total body screening, early surgical intervention, or pharmacologic treatment.
- Risk assessment of asymptomatic family members according to the mode of inheritance
- Reduce the incidence of advanced adenomas at colonoscopy.
- Prevention of CRC.
- Reduce morbidity related to CRC, or morbidity secondary to complications of surveillance and treatment.
- Improved identification of hereditary CRC syndromes.
- Improved pathways from diagnosis to treatment in susceptible populations.
Genes & Diseases
|GENE||OMIM DISEASES||INHERITANCE*||% GENE COVERAGE (20X)||HGMD**|
|AKT1||Cowden Syndrome 6||AD||100||6 of 6|
|APC||Familial Adenomatous Polyposis 1, Desmoid Disease, Gardner Syndrome||AD||98.92||1846 of 1882|
|AXIN2||AXIN2-Related Attenuated Familial Adenomatous Polyposis, Oligodontia-Colorectal Cancer Syndrome||AD||99.86||1608 of 1632|
|ATM||Ataxia-Telangiectasia, Breast Cancer, Mantle Cell Lymphoma||AD.AR||99.93||32 of 33|
|BLM||Bloom Syndrome||AR||97.19||133 of 141|
|BMPR1A||Familial Colorectal Cancer Type X, Juvenile Polyposis Syndrome Of Infancy, Polyposis Syndrome Juvenile Intestinal, Polyposis Syndrome Hereditary Mixed||AD||100||124 of 127|
|BUB1B||Mosaic Variegated Aneuploidy Syndrome||AD, AR||99.84||30 of 31|
|CDH1||Blepharo-Cheilo-Odontic Syndrome, Breast Cancer, Cleft Lip/Palate, Gastric Cancer, Prostate Cancer||AD||100||361 of 363|
|CHEK2||Li-Fraumeni Syndrome, Breast Cancer Susceptibility To, Prostate Cancer Susceptibility To, Colorectal Cancer Susceptibility To||AD||99.47||307 of 310|
|ENG||Familial Cerebral Saccular Aneurysm, Generalized Juvenile Polyposis/Juvenile Polyposis Coli, Hereditary Haemorrhagic Telangiectasia||AD||100||467 of 471|
|EPCAM||Colorectal Cancer, Hereditary Nonpolyposis, Type 8, Lynch Syndrome||AR||99.94||52 of 70|
|FLCN||Birt–Hogg–Dubé Syndrome, Colorectal Cancer, Renal Cell Carcinoma Nonpapillary||AD||100||200 of 205|
|GALNT12||Colorectal Cancer, Susceptibility To, 1||88.97||14 of 15|
|GREM1||Hereditary Mixed Polyposis Syndrome||99.89||5 of 5|
|MLH1||Colorectal Cancer, Hereditary Nonpolyposis, Type 2, Lynch Syndrome, Mismatch Repair Cancer Syndrome, Muir–Torre Syndrome||AD, AR||99.94||1079 of 1118|
|MLH3||Colorectal Cancer, Hereditary Nonpolyposis, Type 7, Endometrial Carcinoma||AD||99.98||32 of 32|
|MSH2||Lynch Syndrome, Mismatch Repair Cancer Syndrome, Muir–Torre Syndrome||AD, AR||99.99||1032 of 1057|
|MSH3||Familial Adenomatous Polyposis 4||AD, AR||99.42||23 of 24|
|MSH6||Colorectal Cancer, Hereditary Nonpolyposis, Type 5, Lynch Syndrome, Mismatch Repair Cancer Syndrome, Muir-Torre Syndrome||AD, AR||99.28||613 of 641|
|MUTYH||Familial Adenomatous Polyposis, 2||AR||100||183 of 183|
|NTHL1||Familial Adenomatous Polyposis 3||AR||100||13 of 13|
|PIK3CA||Cowden Syndrome 5||AD||99.58||54 of 58|
|PMS2||Colorectal Cancer, Hereditary Nonpolyposis, Type 4, Lynch Syndrome, Mismatch Repair Cancer Syndrome||AD, AR||97.17||264 of 285|
|POLD1||Colorectal Cancer, Susceptibility To, 10, Mandibular Hypoplasia, Deafness, Progeroid Features, And Lipodystrophy Syndrome, Polymerase Proofreading-Related Adenomatous Polyposis||AD||100||40 of 41|
|POLE||Colorectal Cancer, Susceptibility To, 12, FILS Syndrome, IMAGE-I Syndrome, Polymerase Proofreading-Related Adenomatous Polyposis||AD, AR||100||100 of 100|
|PTEN||Bannayan-Riley-Ruvalcaba Syndrome, Cowden Syndrome, Hereditary Breast And Ovarian Cancer Syndrome, Juvenile Polyposis Of Infancy, Lhermitte-Duclos Disease, Meningioma, Familial, Susceptibility To, Proteus Syndrome, Proteus-Like Syndrome, Segmental Outgrowth-Lipomatosis-Arteriovenous Malformation-Epidermal Nevus Syndrome||AD||99.97||609 of 629|
|RNF43||Sessile Serrated Polyposis Cancer Syndrome||AD||99.98||13 of 13|
|RPS20||Familial Colorectal Cancer||99.97||1 of 1|
|SMAD4||Juvenile Polyposis/Hereditary Haemorrhagic Telangiectasia Syndrome, Polyposis, Juvenile Intestinal, Myhre Dysplasia, Polyposis, Juvenile Intestinal||AD||99.56||136 of 136|
|STK11||Peutz–Jeghers Syndrome||AD||81.99||456 of 470|
|TP53||Adrenocortical Carcinoma, Paediatric, Basal Cell Carcinoma, Susceptibility To, 7, Bone Marrow Failure Syndrome 5, Breast Cancer, Colorectal Cancer, Familial Pancreatic Carcinoma, Glioma Susceptibility 1, Hereditary Breast And Ovarian Cancer Syndrome, Li–Fraumeni Syndrome, Osteosarcoma, Papilloma Of Choroid Plexus||AD, MU||98.92||557 of 563|
*Inheritance: AD: Autosomal Dominant; AR: Autosomal Recessive; X: X linked; XLR: X linked Recessive; Mi: Mitochondrial; Mu: Multifactorial.
**Number of clinically relevant mutations according to HGMD
Lorans M, Dow E, Macrae FA, Winship IM, Buchanan DD. Update on Hereditary Colorectal Cancer: Improving the Clinical Utility of Multigene Panel Testing. Clin Colorectal Cancer. 2018 Jun;17(2):e293-e305. doi: 10.1016/j.clcc.2018.01.001.
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National Comprehensive Cancer Network. (2021). Retrieved from https://www.nccn.org/professionals/physician_gls/default.aspx#detection
American Cancer Society https://www.cancer.org/cancer/colon-rectal-cancer.html
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