Deepak, a patient with a history of familial polyposis undergoes a diagnostic polypectomy. Which of the following types of polyps is most likely to be found?
a. The earliest mutations in the adenoma-carcinoma sequence occur in the APC gene.
b. The earliest phenotypic change present is known as aberrant crypt formation, and the most consistent genetic aberrations within these cells are abnormally short proteins known as APC truncations.
c. Most clinically relevant derangements in APC are truncation mutations created by inappropriate transcription of premature termination codons.
d. A germline APC truncation mutation is responsible for the autosomal dominant–inherited disease, FAP.
e. Thirty percent of cases of FAP are de novo germline mutations, thus presenting without a family history of the disease.
f. It is classically characterized by greater than 100 adenomatous polyps present in the colon and rectum.
g. These polyps often number in the thousands and are almost always manifest by the late second or early third decade of life.
h. FAP is of great interest to those studying sporadic colorectal cancer because APC truncation mutations similar to those found in APC patients occur in 85% of sporadic colorectal cancers.
i. Most APC truncation mutations occur in the mutational cluster region of the gene, an area responsible for β-catenin binding.
j. Classic FAP is characterized by truncation mutations occurring in the gene from codon 1250 to codon 1464. Mutations occurring further along the gene toward the 3′ end are quite rare and most likely result in either a much attenuated phenotype or no detectable abnormality
k. The variability of the FAP phenotype is also demonstrated by the presence or absence of extraintestinal manifestations of disease.