{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T12:11:14Z","timestamp":1779192674250,"version":"3.51.4"},"reference-count":39,"publisher":"SAGE Publications","issue":"12","license":[{"start":{"date-parts":[[2016,10,5]],"date-time":"2016-10-05T00:00:00Z","timestamp":1475625600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Genetic Testing and Molecular Biomarkers"],"published-print":{"date-parts":[[2016,12,1]]},"abstract":"\n Aims:<\/jats:italic>\n Colorectal adenomatous polyposis entailing cancer predisposition is caused by constitutional mutations in different genes.\n APC<\/jats:italic>\n is associated with the familial adenomatous polyposis (FAP\/AFAP) and\n MUTYH<\/jats:italic>\n with the\n MUTYH<\/jats:italic>\n -associated polyposis (MAP), while\n POLE<\/jats:italic>\n and\n POLD1<\/jats:italic>\n mutations cause the polymerase proofreading-associated polyposis (PPAP).\n Methods:<\/jats:italic>\n We screened for mutations in patients with multiple adenomas\/FAP: 121 patients were analyzed for\n APC<\/jats:italic>\n and\n MUTYH<\/jats:italic>\n mutations, and 36 patients were also evaluated for\n POLE<\/jats:italic>\n and\n POLD1<\/jats:italic>\n gene mutations.\n Results:<\/jats:italic>\n We found 20 FAP\/AFAP, 15 MAP, and no PPAP subjects: pathogenic mutations proved to be heterogeneous, and included 5\n APC<\/jats:italic>\n and 1\n MUTYH<\/jats:italic>\n novel mutations. The mutation detection rate was significantly different between patients with 5-100 polyps and those with >100 polyps (\n p<\/jats:italic>\n \u2009=\u20098.154\u2009\u00d7\u200910\n \u22127<\/jats:sup>\n ), with\n APC<\/jats:italic>\n mutations being associated with an aggressive phenotype (\n p<\/jats:italic>\n \u2009=\u20091.279\u2009\u00d7\u200910\n \u22129<\/jats:sup>\n ). Mean age at diagnosis was lower in FAP\/AFAP compared to MAP (\n p<\/jats:italic>\n \u2009=\u20093.055\u2009\u00d7\u200910\n \u22124<\/jats:sup>\n ). Mutation-negative probands showed a mean age at diagnosis that was significantly higher than FAP\/AFAP (\n p<\/jats:italic>\n \u2009=\u20093.46986\u2009\u00d7\u200910\n \u22127<\/jats:sup>\n ) and included 45.3% of patients with <30 polyps and 70.9% of patients with no family history.\n Conclusions:<\/jats:italic>\n This study enlarges the\n APC<\/jats:italic>\n and\n MUTYH<\/jats:italic>\n mutational spectra, and also evaluated variants of uncertain significance, including the MUTYH p.Gln338His mutation. Moreover this study underscores the phenotypic heterogeneity and genotype-phenotype correlations in a cohort of Italian patients.\n <\/jats:p>","DOI":"10.1089\/gtmb.2016.0198","type":"journal-article","created":{"date-parts":[[2016,10,5]],"date-time":"2016-10-05T10:53:47Z","timestamp":1475664827000},"page":"777-785","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["Colorectal Adenomatous Polyposis: Heterogeneity of Susceptibility Gene Mutations and Phenotypes in a Cohort of Italian Patients"],"prefix":"10.1177","volume":"20","author":[{"given":"Monica","family":"Marabelli","sequence":"first","affiliation":[{"name":"University of Pavia","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeria","family":"Molinaro","sequence":"additional","affiliation":[{"name":"University of Pavia","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raefa Abou","family":"Khouzam","sequence":"additional","affiliation":[{"name":"University of Pavia","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrico","family":"Berrino","sequence":"additional","affiliation":[{"name":"Candiolo Cancer Institute","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mara","family":"Panero","sequence":"additional","affiliation":[{"name":"Candiolo Cancer Institute","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonella","family":"Balsamo","sequence":"additional","affiliation":[{"name":"Candiolo Cancer Institute","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiziana","family":"Venesio","sequence":"additional","affiliation":[{"name":"Candiolo Cancer Institute","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guglielmina Nadia","family":"Ranzani","sequence":"additional","affiliation":[{"name":"University of Pavia","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2016,10,5]]},"reference":[{"key":"e_1_3_3_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.9370"},{"key":"e_1_3_3_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-015-0244-4"},{"key":"e_1_3_3_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2015.08.001"},{"key":"e_1_3_3_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2012.09.016"},{"key":"e_1_3_3_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e31815bf940"},{"key":"e_1_3_3_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2014.74"},{"key":"e_1_3_3_8_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.12.050"},{"key":"e_1_3_3_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10151-012-0887-5"},{"key":"e_1_3_3_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.20054"},{"key":"e_1_3_3_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2012.8780"},{"key":"e_1_3_3_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-4-22"},{"key":"e_1_3_3_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2013-102000"},{"key":"e_1_3_3_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2263"},{"key":"e_1_3_3_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756-9966-27-49"},{"key":"e_1_3_3_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2012.07.005"},{"key":"e_1_3_3_17_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.21.6853"},{"key":"e_1_3_3_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36253"},{"key":"e_1_3_3_19_1","doi-asserted-by":"publisher","DOI":"10.1086\/301890"},{"key":"e_1_3_3_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2503"},{"key":"e_1_3_3_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0072091"},{"key":"e_1_3_3_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2010.01.013"},{"key":"e_1_3_3_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.27761"},{"key":"e_1_3_3_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgs270"},{"key":"e_1_3_3_25_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.14.712"},{"key":"e_1_3_3_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.22314"},{"key":"e_1_3_3_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22082"},{"key":"e_1_3_3_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2014.435"},{"key":"e_1_3_3_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2007.00694.x"},{"key":"e_1_3_3_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6605966"},{"key":"e_1_3_3_31_1","doi-asserted-by":"publisher","DOI":"10.1177\/0004563215597944"},{"key":"e_1_3_3_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt130"},{"key":"e_1_3_3_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2012.00083"},{"key":"e_1_3_3_34_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.LAB.0000106722.37873.8D"},{"key":"e_1_3_3_35_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.MP.0000042421.83775.0E"},{"key":"e_1_3_3_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-006-0127-4"},{"key":"e_1_3_3_37_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.02.022"},{"key":"e_1_3_3_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3287"},{"key":"e_1_3_3_39_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.01.022"},{"key":"e_1_3_3_40_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.05.006"}],"container-title":["Genetic Testing and Molecular Biomarkers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/gtmb.2016.0198","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/gtmb.2016.0198","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/gtmb.2016.0198","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T12:03:07Z","timestamp":1779192187000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/gtmb.2016.0198"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,10,5]]},"references-count":39,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2016,12,1]]}},"alternative-id":["10.1089\/gtmb.2016.0198"],"URL":"https:\/\/doi.org\/10.1089\/gtmb.2016.0198","relation":{},"ISSN":["1945-0265","1945-0257"],"issn-type":[{"value":"1945-0265","type":"print"},{"value":"1945-0257","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,10,5]]}}}