Brain tumor–polyposis (BTP) syndrome

Brain tumor–polyposis (BTP) syndrome is a rare genetic disease characterized clinically by the concurrence of multiple colorectal adenomas and primary brain tumors. The BTP syndromes can be subdivided into two major categories based upon clinical phenotype, modes of inheritance and underlying gene mutations. Type I BTP syndrome (Turcot's syndrome) is characterized by the presence of malignant gliomas and multiple benign colorectal adenomas in the second or third decade. The frequent presence of consanguinity and the absence of parental disease indicate that Type I BTP syndrome is inherited in an autosomal recessive manner. The genes responsible for Type I BTP syndrome include the mismatch repair (MMR) genes, which are also linked to hereditary nonpolyposis colorectal cancer (HNPCC, or Lynch syndrome). The original BTP case described by Turcot fits into this category. In contrast, a second, Type II BTP syndrome (Crail's syndrome) typically presents with a medulloblastoma instead of astrocytic tumors, and the number and size of colonic polyps is similar to those in familial adenomatous polyposis (FAP). In this syndrome, colorectal polyposis usually occurs in multiple generations and evidence for consanguinity is lacking, indicative of an autosomal dominant mode of inheritance. Adenomatous polyposis coli (APC) tumor suppressor gene germ-line mutations have been found in most cases of Type II BTP syndrome patients. Also, FAP patients have a significant increase in the relative risk of developing a medulloblastoma compared to the general population. Therefore, Type II BTP syndrome may represent a manifestation of the APC gene defect in FAP families, as first described by Crail. Interestingly, APC somatic mutations are found in most sporadic colorectal adenomas as well as in a smaller fraction of sporadic medulloblastomas without associated FAP or BTP syndromes. Further illustration of the molecular mechanism of tumorigenesis, both of colorectal and primary brain tumors in BTP syndrome, will provide useful diagnostic and prognostic information and will elucidate important mechanisms in the more common sporadic forms of brain and colon tumors.