title: APC I1307K mutations and forkhead box gene (FOXO1A): another piece of an interesting correlation.
abstract: OBJECTIVE
  Germline nonsense and frameshift mutations in the adenomatous polyposis coli (APC) gene are found in approximately 90% of individuals affected by familial adenomatous polyposis (FAP) and a genotype-phenotype relationship has been observed. Missense mutations have also been found in a few cases, even if their role in FAP is still unknown. An association between a missense mutation, APC I1307K, and the risk of sporadic colorectal cancer (CRC) has been reported. In order to improve the knowledge about the genetic effect of APC I1307K on the phenotype, we tried a new approach using matrix-assisted laser desorption/ionization mass spectrometry (MALDI/MS).
  
  
  METHODS
  An APC mutation (I1307K) was found in an index case of a non-Jewish woman and her son with attenuated familial adenomatous polyposis (A-FAP) and no family history of cancer. In order to evaluate whether the presence and abundance of the ionic species are related to the presence of cancer or the presence of mutation, comparative analyses of 11 healthy clean-colon subjects, 59 patients with CRC (stage II n=19, stage III n=23, stage IV n=17) without polyps, and 9 FAP patients, carriers of a nonsense mutation in the APC gene, were evaluated.
  
  
  RESULTS
  Comparative analysis of serum protein profiles of the index patient and her healthy son, FAP and sporadic CRC patients, and subjects with preneoplastic lesions showed a characteristic abundance of ionic species at m/z 905, which was not present in healthy controls. Two peptides were identified from MALDI/MS/MS spectra of m/z 905 belonging to the kininogen-1 precursor and the human forkhead box protein 01A (FOXO1A). FOXO1A was present in only two subjects carrying I1307K, but not in other patients.
  
  
  CONCLUSIONS
  Our findings seem to suggest a relationship between m/z 905, FOXO1A and the development and growth of colorectal cancer. FOXO1A fragment determination in serum with MALDI/MS might be a promising approach for early detection of colon carcinoma or for the development of targeted therapies.
authors.affiliation: Department of Surgical, Oncological and Gastroenterological Sciences, 2nd Surgical Clinic, University of Padua, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Agostini
authors.forename: Chiara
authors.initials: C
authors.lastname: Bedin
authors.forename: Salvatore
authors.initials: S
authors.lastname: Pucciarelli
authors.forename: Mariavittoria
authors.initials: M
authors.lastname: Enzo
authors.forename: Marta
authors.initials: M
authors.lastname: Briarava
authors.forename: Roberta
authors.initials: R
authors.lastname: Seraglia
authors.forename: Eugenio
authors.initials: E
authors.lastname: Ragazzi
authors.forename: Pietro
authors.initials: P
authors.lastname: Traldi
authors.forename: Laura
authors.initials: L
authors.lastname: Molin
authors.forename: Emanuele Damiano
authors.initials: ED
authors.lastname: Urso
authors.forename: Isabella
authors.initials: I
authors.lastname: Mammi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Viel
authors.forename: Mario
authors.initials: M
authors.lastname: Lise
authors.forename: Ennio
authors.initials: E
authors.lastname: Tasciotti
authors.forename: Alessandra
authors.initials: A
authors.lastname: Biasiolo
authors.forename: Patrizia
authors.initials: P
authors.lastname: Pontisso
authors.forename: Donato
authors.initials: D
authors.lastname: Nitti
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D018389:Codon, Nonsense; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics*; D017491:Genes, APC; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D017422:Sequence Analysis, DNA; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D055815:Young Adult
chemical_list: C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein; D018389:Codon, Nonsense; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors