Published online Aug 21, 2015. doi: 10.3748/wjg.v21.i31.9413
Peer-review started: July 25, 2014
First decision: September 3, 2014
Revised: May 21, 2015
Accepted: June 16, 2015
Article in press: June 16, 2015
Published online: August 21, 2015
AIM: To characterize APC gene mutations and correlate them with patient phenotypes in individuals diagnosed with familial adenomatous polyposis (FAP) in northern Brazil.
METHODS: A total of 15 individuals diagnosed with FAP from 5 different families from the north of Brazil were analyzed in this study. In addition to patients with histopathological diagnosis of FAP, family members who had not developed the disease were also tested in order to identify mutations and for possible genetic counseling. All analyzed patients or their guardians signed a consent form approved by the Research Ethics Committee of the João de Barros Barreto University Hospital (Belem, Brazil). DNA extracted from the peripheral blood of a member of each of the affected families was subjected to direct sequencing. The proband of each family was sequenced to identify germline mutations using the Ion Torrent platform. To validate the detected mutations, Sanger sequencing was also performed. The samples from all patients were also tested for the identification of mutations by real-time quantitative polymerase chain reaction using the amplification refractory mutation system.
RESULTS: Through interviews with relatives and a search of medical records, it was possible to construct genograms for three of the five families included in the study. All 15 patients from the five families with FAP exhibited mutations in the APC gene, and all mutations were detected in exon 15 of the APC gene. In addition to the patients with a histological diagnosis of FAP, family members without disease symptoms showed the mutation in the APC gene. In the present study, we detected two of the three most frequent germline mutations in the literature: the mutation at codon 1309 and the mutation at codon 1061. The presence of c.3956delC mutation was found in all families from this study, and suggests that this mutation was introduced in the population of the State of Pará through ancestor immigration (i.e., a de novo mutation that arose in one member belonging to this state from Brazil).
CONCLUSION: Regardless of its origin, the c.3956delC mutation is a strong candidate biomarker of this hereditary cancer syndrome in families of northern Brazil.
Core tip: In the northern region of Brazil, gastrointestinal tumors are the second most frequent type of cancer among men and the third most frequent among women. These tumors are considered a serious public health problem because they are often diagnosed in advanced stages and have extremely low survival rates. Evaluation of family history to determine the number of relatives affected and genetic screening analysis are important preventive measures to assist in the early diagnosis of patients who have not yet developed the disease, as was the case of some patients analyzed in this study.