{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T05:24:57Z","timestamp":1787117097295,"version":"build-2736575974"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Familial adenomatous polyposis (FAP) is a severe autosomal dominant hereditary cancer syndrome. Patients develop hundreds of adenomatous polyps throughout the colon with the risk of colorectal cancer, if untreated, approaching 100%. FAP is caused by pathogenic germline variants in the\n                      <jats:italic>APC<\/jats:italic>\n                      gene. Deletions in the\n                      <jats:italic>APC<\/jats:italic>\n                      1B promoter cause FAP in a small subgroup of patients. Previous studies suggested that the\n                      <jats:italic>APC<\/jats:italic>\n                      promoter deletions in unrelated FAP patients from the US and Italy are identical and may thus have spread from a single founder. The aim of this study was to investigate whether a similar founder effect can be detected in the Russian population.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and methods<\/jats:title>\n                    <jats:p>\n                      We performed whole-genome sequencing on five unrelated patients (three males and two females) with extensive (over 100) colon polyps, family history of FAP, and germline\n                      <jats:italic>APC<\/jats:italic>\n                      1B promoter deletions previously detected by the multiplex ligation-dependent probe amplification (MLPA) and detected precise deletion boundaries.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The patients carried deletions in the\n                      <jats:italic>APC<\/jats:italic>\n                      1B promoter ranging from ~3 to ~122 kbp. We found no association between the deletion size and either the age of the onset or severity of the disease. All deletions were unique and no identical deletion boundaries were observed. However, in four patients, the right deletion breakpoints fell into a 1 kbp region downstream of the 1B promoter. The right breakpoints of several deletions detected in FAP patients from other countries also fell into this narrow region.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic>APC<\/jats:italic>\n                      1B promoter deletions analyzed in this study had arisen independently and there is thus no evidence of a founder effect. Therefore, at least for the cohort of FAP patients with\n                      <jats:italic>APC<\/jats:italic>\n                      1B promoter deletions studied here, WGS did not provide an added diagnostic benefit to MLPA aside from precisely determining the deletion breakpoints.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1834702","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T04:36:34Z","timestamp":1787114194000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Analysis of APC promoter 1B deletions in Russian families with familial adenomatous polyposis"],"prefix":"10.3389","volume":"16","author":[{"given":"Aleksey S.","family":"Tsukanov","sequence":"first","affiliation":[{"name":"Ryzhikh National Medical Research Centre for Coloproctology","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey I.","family":"Achkasov","sequence":"additional","affiliation":[{"name":"Ryzhikh National Medical Research Centre for Coloproctology","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna N.","family":"Loginova","sequence":"additional","affiliation":[{"name":"Ryzhikh National Medical Research Centre for Coloproctology","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry Yu.","family":"Pikunov","sequence":"additional","affiliation":[{"name":"Ryzhikh National Medical Research Centre for Coloproctology","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitaly P.","family":"Shubin","sequence":"additional","affiliation":[{"name":"Ryzhikh National Medical Research Centre for Coloproctology","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra S.","family":"Monakhova","sequence":"additional","affiliation":[{"name":"Biotechnology campus LLC","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasiia V.","family":"Kashchenko","sequence":"additional","affiliation":[{"name":"Biotechnology campus LLC","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulia M.","family":"Suvorova","sequence":"additional","affiliation":[{"name":"Biotechnology campus LLC","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evgeny I.","family":"Klimuk","sequence":"additional","affiliation":[{"name":"Biotechnology campus LLC","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantin V.","family":"Severinov","sequence":"additional","affiliation":[{"name":"Biotechnology campus LLC","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"10","DOI":"10.33878\/2073-7556-2022-21-2-10-24","article-title":"Adenomatous polyposis syndrome","volume":"21","author":"Shelygin","year":"2022","journal-title":"Koloproktologia"},{"key":"B2","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1007\/BF00342466","article-title":"The incidence rate of familial adenomatous polyposis. Results from the Danish Polyposis Register","volume":"11","author":"B\u00fclow","year":"1996","journal-title":"Int J Colorectal Dis"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.23768","article-title":"Mutational screening through comprehensive bioinformatics analysis to detect novel germline mutations in the APC gene in patients with familial adenomatous polyposis (FAP)","volume":"35","author":"Ghadamyari","year":"2021","journal-title":"J Clin Lab Anal"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1093\/bjs\/znae070","article-title":"Updated European guidelines for clinical management of familial adenomatous polyposis (FAP), MUTYH-associated polyposis (MAP), gastric adenocarcinoma, proximal polyposis of the stomach (GAPPS) and other rare adenomatous polyposis syndromes: a joint EHTG-ESCP revision","volume":"111","author":"Zaffaroni","year":"2024","journal-title":"Br J Surg"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2017.212","article-title":"Hereditary colorectal polyposis and cancer syndromes: a primer on diagnosis and management","volume":"112","author":"Kanth","year":"2017","journal-title":"Am J Gastroenterol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"59","DOI":"10.22416\/1382-4376-2023-33-1-59-67","article-title":"Large rearrangements in genes responsible for familial adenomatous polyposis, MUTYH-associated polyposis and Peutz\u2013Jeghers syndrome in Russian patients","volume":"33","author":"Loginova","year":"2023","journal-title":"Russ J Gastroenterol Hepatol Coloproctology"},{"key":"B7","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.jmoldx.2012.07.005","article-title":"APC germline mutations in individuals being evaluated for familial adenomatous polyposis: a review of the Mayo Clinic experience with 1591 consecutive tests","volume":"15","author":"Kerr","year":"2013","journal-title":"J Mol Diagn JMD"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v16.i12.1522","article-title":"APC gene mutations in Chinese familial adenomatous polyposis patients","volume":"16","author":"Sheng","year":"2010","journal-title":"World J Gastroenterol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12503","article-title":"APC promoter 1B deletion in seven American families with familial adenomatous polyposis","volume":"88","author":"Snow","year":"2015","journal-title":"Clin Genet"},{"key":"B10","doi-asserted-by":"publisher","first-page":"170","DOI":"10.12688\/f1000research.6636.1","article-title":"Characterization of an APC Promoter 1B deletion in a patient diagnosed with familial adenomatous polyposis via whole genome shotgun sequencing","volume":"4","author":"Kalbfleisch","year":"2015","journal-title":"F1000Research"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.22488","article-title":"A novel APC promoter 1B deletion shows a founder effect in Italian patients with classical familial adenomatous polyposis phenotype","volume":"56","author":"Marabelli","year":"2017","journal-title":"Genes Chromosomes Cancer"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.14806\/ej.17.1.200","article-title":"Cutadapt removes adapter sequences from high-throughput sequencing reads","volume":"17","author":"Martin","year":"2011","journal-title":"EMBnetjournal"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.48550\/arXiv.1303.3997","article-title":"Aligning sequence reads, clone sequences and assembly contigs with BWAMEM","author":"Li","year":"2013","journal-title":"arXiv preprint"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv710","article-title":"Manta: rapid detection of structural variants and indels for germline and cancer sequencing applications","volume":"32","author":"Chen","year":"2016","journal-title":"Bioinformatics"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1101\/gr.849004","article-title":"WebLogo: a sequence logo generator","volume":"14","author":"Crooks","year":"2004","journal-title":"Genome Res"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/srep26011","article-title":"Reduced expression of APC-1B but not APC-1A by the deletion of promoter 1B is responsible for familial adenomatous polyposis","volume":"6","author":"Yamaguchi","year":"2016","journal-title":"Sci Rep"},{"key":"B17","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/s13073-015-0148-0","article-title":"Novel APC promoter and exon 1B deletion and allelic silencing in three mutation-negative classic familial adenomatous polyposis families","volume":"7","author":"Lin","year":"2015","journal-title":"Genome Med"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2011.201","article-title":"Inactivation of promoter 1B of APC causes partial gene silencing: evidence for a significant role of the promoter in regulation and causative of familial adenomatous polyposis","volume":"30","author":"Rohlin","year":"2011","journal-title":"Oncogene"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.22197","article-title":"Promoter-specific alterations of APC are a rare cause for mutation-negative familial adenomatous polyposis","volume":"53","author":"Pavicic","year":"2014","journal-title":"Genes Chromosomes Cancer"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12210","article-title":"APC promoter 1B deletion in familial polyposis\u2014implications for mutation\u2010negative families","volume":"85","author":"Kadiyska","year":"2014","journal-title":"Clin Genet"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygeno.2025.111119","article-title":"Identifying and characterizing a novel APC promoter 1B deletion in a Chinese family with familial adenomatous polyposis","volume":"117","author":"Ai","year":"2025","journal-title":"Genomics"},{"key":"B22","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.mgene.2015.12.005","article-title":"Copy number variants associated with 18p11.32, DCC and the promoter 1B region of APC in colorectal polyposis patients","volume":"7","author":"Masson","year":"2016","journal-title":"Meta Gene"},{"key":"B23","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.cancergen.2022.02.002","article-title":"Necessity of multiplex ligation probe amplification in genetic tests: Germline variant analysis of the APC gene in familial adenomatous polyposis patients","author":"Lee","year":"2022","journal-title":"Cancer Genet"},{"key":"B24","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1007\/s10689-015-9845-5","article-title":"Contribution of APC and MUTYH mutations to familial adenomatous polyposis susceptibility in Hungary","volume":"15","author":"Papp","year":"2016","journal-title":"Fam Cancer"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-8-54","article-title":"Mutational spectrum of the APC and MUTYH genes and genotype-phenotype correlations in Brazilian FAP, AFAP, and MAP patients","volume":"8","author":"Torrezan","year":"2013","journal-title":"Orphanet J Rare Dis"},{"key":"B26","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1186\/1897-4287-3-3-95","article-title":"Familial adenomatous polyposis: experience from a study of 1164 unrelated German polyposis patients","volume":"3","author":"Friedl","year":"2005","journal-title":"Hered Cancer Clin Pract"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1834702\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T04:36:39Z","timestamp":1787114199000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1834702\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,19]]},"references-count":26,"alternative-id":["10.3389\/fonc.2026.1834702"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2026.1834702","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,19]]},"article-number":"1834702"}}