Hereditary Colorectal Cancer Panel

Colorectal cancer (CRC) is the third most common cancer diagnosis in the United States and approximately 5% are the result of a hereditary colorectal cancer syndrome. The features suggestive of a hereditary CRC predisposition include: young age at diagnosis, history of CRC or adenomatous polyps in one or more close relative, multiple primary cancers in a single individual, and several relatives affected with cancer spanning multiple generations. Hereditary CRC are generally divided into two subgroups: (1) polyposis (including familial adenomatous polyposis (FAP) and attenuated FAP (AFAP), which are caused by pathogenic variants in the APC gene; and MUTYH-associated polyposis, which is caused by pathogenic variants in the MUTYH gene; and (2) Lynch syndrome (often referred to as hereditary nonpolyposis colorectal cancer), which is caused by germline pathogenic variants in DNA mismatch repair genes  (MLH1, MSH2, MSH6, and PMS2) and EPCAM. Other CRC syndromes and their associated genes include oligopolyposis (POLE, POLD1), NTHL1, juvenile polyposis syndrome (BMPR1A, SMAD4), Cowden syndrome (PTEN), and Peutz-Jeghers syndrome (STK11). Many of these syndromes are also associated with extracolonic cancers and other manifestations. This comprehensive panel includes genes associated with Lynch syndrome, FAP, and AFAP, as well as other genes known to increase risk for colorectal polyps and CRC. This test is specifically designed to detect germline pathogenic variants and is not appropriate for the detection of somatic variants in tumor tissue. The panel includes sequence and deletion/duplication analysis of all the listed genes.