APCI1307K mutations and forkhead box gene (FOXO1A): Another piece of an interesting correlation

Marco Agostini, Chiara Bedin, Salvatore Pucciarelli, Mariavittoria Enzo, Marta Briarava, Roberta Seraglia, Eugenio Ragazzi, Pietro Traldi, Laura Molin, Emanuele Damiano Urso, Isabella Mammi, Alessandra Viel, Mario Lise, Ennio Tasciotti, Alessandra Biasiolo, Patrizia Pontisso, Donato Nitti

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Purpose: Germline nonsense and frame shift 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). Experimental design: 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.

Original languageEnglish (US)
Pages (from-to)13-19
Number of pages7
JournalInternational Journal of Biological Markers
Volume27
Issue number1
DOIs
StatePublished - Jan 1 2012

Keywords

  • APC I1307K
  • Colorectal cancer
  • FOXO1A

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cancer Research
  • Oncology
  • Pathology and Forensic Medicine
  • Medicine(all)

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