TY - JOUR
T1 - APCI1307K mutations and forkhead box gene (FOXO1A)
T2 - Another piece of an interesting correlation
AU - Agostini, Marco
AU - Bedin, Chiara
AU - Pucciarelli, Salvatore
AU - Enzo, Mariavittoria
AU - Briarava, Marta
AU - Seraglia, Roberta
AU - Ragazzi, Eugenio
AU - Traldi, Pietro
AU - Molin, Laura
AU - Urso, Emanuele Damiano
AU - Mammi, Isabella
AU - Viel, Alessandra
AU - Lise, Mario
AU - Tasciotti, Ennio
AU - Biasiolo, Alessandra
AU - Pontisso, Patrizia
AU - Nitti, Donato
PY - 2012/1
Y1 - 2012/1
N2 - 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.
AB - 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.
KW - APC I1307K
KW - Colorectal cancer
KW - FOXO1A
UR - http://www.scopus.com/inward/record.url?scp=84863895250&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84863895250&partnerID=8YFLogxK
U2 - 10.5301/JBM.2011.8908
DO - 10.5301/JBM.2011.8908
M3 - Article
C2 - 22180177
AN - SCOPUS:84863895250
SN - 0393-6155
VL - 27
SP - 13
EP - 19
JO - International Journal of Biological Markers
JF - International Journal of Biological Markers
IS - 1
ER -