{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:08:32Z","timestamp":1790842112273,"version":"4.1.0"},"reference-count":32,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T00:00:00Z","timestamp":1730678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto Portugu\u00eas de Oncologia de Lisboa, E.P.E.\u2014","award":["UIC\/829"],"award-info":[{"award-number":["UIC\/829"]}]},{"name":"Instituto Portugu\u00eas de Oncologia de Lisboa, E.P.E.\u2014","award":["UIDB\/04462\/2020"],"award-info":[{"award-number":["UIDB\/04462\/2020"]}]},{"name":"Instituto Portugu\u00eas de Oncologia de Lisboa, E.P.E.\u2014","award":["UIDP\/04462\/2020"],"award-info":[{"award-number":["UIDP\/04462\/2020"]}]},{"name":"Instituto Portugu\u00eas de Oncologia de Lisboa, E.P.E.\u2014","award":["LA\/P\/0087\/2020"],"award-info":[{"award-number":["LA\/P\/0087\/2020"]}]},{"name":"Liga Portuguesa Contra o Cancro-N\u00facleo Regional do Sul","award":["UIC\/829"],"award-info":[{"award-number":["UIC\/829"]}]},{"name":"Liga Portuguesa Contra o Cancro-N\u00facleo Regional do Sul","award":["UIDB\/04462\/2020"],"award-info":[{"award-number":["UIDB\/04462\/2020"]}]},{"name":"Liga Portuguesa Contra o Cancro-N\u00facleo Regional do Sul","award":["UIDP\/04462\/2020"],"award-info":[{"award-number":["UIDP\/04462\/2020"]}]},{"name":"Liga Portuguesa Contra o Cancro-N\u00facleo Regional do Sul","award":["LA\/P\/0087\/2020"],"award-info":[{"award-number":["LA\/P\/0087\/2020"]}]},{"name":"Televis\u00e3o Independente, S.A","award":["UIC\/829"],"award-info":[{"award-number":["UIC\/829"]}]},{"name":"Televis\u00e3o Independente, S.A","award":["UIDB\/04462\/2020"],"award-info":[{"award-number":["UIDB\/04462\/2020"]}]},{"name":"Televis\u00e3o Independente, S.A","award":["UIDP\/04462\/2020"],"award-info":[{"award-number":["UIDP\/04462\/2020"]}]},{"name":"Televis\u00e3o Independente, S.A","award":["LA\/P\/0087\/2020"],"award-info":[{"award-number":["LA\/P\/0087\/2020"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT), Minist\u00e9rio da Ci\u00eancia, Tecnologia e Ensino Superior (MCTES), Portugal","award":["UIC\/829"],"award-info":[{"award-number":["UIC\/829"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT), Minist\u00e9rio da Ci\u00eancia, Tecnologia e Ensino Superior (MCTES), Portugal","award":["UIDB\/04462\/2020"],"award-info":[{"award-number":["UIDB\/04462\/2020"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT), Minist\u00e9rio da Ci\u00eancia, Tecnologia e Ensino Superior (MCTES), Portugal","award":["UIDP\/04462\/2020"],"award-info":[{"award-number":["UIDP\/04462\/2020"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT), Minist\u00e9rio da Ci\u00eancia, Tecnologia e Ensino Superior (MCTES), Portugal","award":["LA\/P\/0087\/2020"],"award-info":[{"award-number":["LA\/P\/0087\/2020"]}]},{"name":"iNOVA4Health R&amp;D Unit","award":["UIC\/829"],"award-info":[{"award-number":["UIC\/829"]}]},{"name":"iNOVA4Health R&amp;D Unit","award":["UIDB\/04462\/2020"],"award-info":[{"award-number":["UIDB\/04462\/2020"]}]},{"name":"iNOVA4Health R&amp;D Unit","award":["UIDP\/04462\/2020"],"award-info":[{"award-number":["UIDP\/04462\/2020"]}]},{"name":"iNOVA4Health R&amp;D Unit","award":["LA\/P\/0087\/2020"],"award-info":[{"award-number":["LA\/P\/0087\/2020"]}]},{"name":"iNOVA4Health R&amp;D Unit","award":["UIC\/829"],"award-info":[{"award-number":["UIC\/829"]}]},{"name":"iNOVA4Health R&amp;D Unit","award":["UIDB\/04462\/2020"],"award-info":[{"award-number":["UIDB\/04462\/2020"]}]},{"name":"iNOVA4Health R&amp;D Unit","award":["UIDP\/04462\/2020"],"award-info":[{"award-number":["UIDP\/04462\/2020"]}]},{"name":"iNOVA4Health R&amp;D Unit","award":["LA\/P\/0087\/2020"],"award-info":[{"award-number":["LA\/P\/0087\/2020"]}]},{"name":"Associated Laboratory LS4FUTURE","award":["UIC\/829"],"award-info":[{"award-number":["UIC\/829"]}]},{"name":"Associated Laboratory LS4FUTURE","award":["UIDB\/04462\/2020"],"award-info":[{"award-number":["UIDB\/04462\/2020"]}]},{"name":"Associated Laboratory LS4FUTURE","award":["UIDP\/04462\/2020"],"award-info":[{"award-number":["UIDP\/04462\/2020"]}]},{"name":"Associated Laboratory LS4FUTURE","award":["LA\/P\/0087\/2020"],"award-info":[{"award-number":["LA\/P\/0087\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Serrated polyposis syndrome (SPS) is characterized by the development of multiple colorectal serrated polyps and increased predisposition to colorectal cancer (CRC). However, the molecular basis of SPS, especially in cases presenting family history of SPS and\/or polyps and\/or CRC in first-degree relatives (SPS-FHP\/CRC), is still poorly understood. In a previous study, we proposed the existence of two molecular entities amongst SPS-FHP\/CRC families, proximal\/whole-colon and distal SPS-FHP\/CRC, according to the preferential location of lesions and somatic events involved in tumor initiation. In the present study, we aimed to investigate these distinct subgroups of SPS patients in a larger cohort at the germline level and to identify the genetic defects underlying an inherited susceptibility for these two entities. Next-generation sequencing was performed using multigene analysis with a custom-designed panel in a Miseq platform in 60 SPS patients (with and without\/unknown FHP\/CRC). We found germline pathogenic variants in 6\/60 patients (ATM, FANCM, MITF, RAD50, RAD51C, and RNF43). We also found variants of unknown significance (VUS), with prediction of probable damaging effect in 23\/60 patients (ATM, BLM, BRCA1, FAN1, ERCC2, ERCC3, FANCA, FANCD2, FANCL, MSH2, MSH6, NTHL1, PALB2, PDGFRA, PMS2, PTCH1, RAD51C, RAD51D, RECQL4, TSC2, WRN, and XRCC5 genes). Most variants were detected in gene coding for proteins of the Fanconi Anemia (FA) pathway involved in the DNA Interstrand-Cross Link repair (ICLR). Notably, variants in ICLR genes were significantly more frequent in the proximal\/whole-colon than in the distal subgroup [15\/44 (34%) vs 1\/16 (6%), p = 0.025], as opposed to the non-ICLR genes that were slightly more frequent in the distal group [8\/44 (18%) vs. 5\/16 (31%), p &gt; 0.05]. Germline defects in the DNA-ICLR genes may contribute to increased serrated colorectal polyps\/carcinoma risk in SPS patients, particularly in proximal\/whole-colon SPS. The inclusion of DNA-ICLR genes in the genetic diagnosis of SPS patients, mainly in those with proximal\/whole-colon lesions, should be considered and validated by other studies. In addition, patients with germline defects in the DNA-ICLR genes may be more sensitive to treatment with platinum-based therapeutics, which can have implications in the clinical management of these patients.<\/jats:p>","DOI":"10.3390\/ijms252111848","type":"journal-article","created":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T09:52:54Z","timestamp":1730713974000},"page":"11848","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Germline Variants in DNA Interstrand-Cross Link Repair Genes May Contribute to Increased Susceptibility for Serrated Polyposis Syndrome"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3713-8770","authenticated-orcid":false,"given":"Patr\u00edcia","family":"Silva","sequence":"first","affiliation":[{"name":"Molecular Pathobiology Research Unit (UIPM), Instituto Portugu\u00eas de Oncologia de Lisboa Francisco Gentil E.P.E. (IPOLFG, EPE), Rua Professor Lima Basto, 1099-023 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0214-5524","authenticated-orcid":false,"given":"In\u00eas","family":"Francisco","sequence":"additional","affiliation":[{"name":"Molecular Pathobiology Research Unit (UIPM), Instituto Portugu\u00eas de Oncologia de Lisboa Francisco Gentil E.P.E. (IPOLFG, EPE), Rua Professor Lima Basto, 1099-023 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3984-6885","authenticated-orcid":false,"given":"Bruno","family":"Filipe","sequence":"additional","affiliation":[{"name":"Molecular Pathobiology Research Unit (UIPM), Instituto Portugu\u00eas de Oncologia de Lisboa Francisco Gentil E.P.E. (IPOLFG, EPE), Rua Professor Lima Basto, 1099-023 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2408-6211","authenticated-orcid":false,"given":"Pedro","family":"Lage","sequence":"additional","affiliation":[{"name":"Gastroenterology Department, Instituto Portugu\u00eas de Oncologia de Lisboa Francisco Gentil E.P.E. (IPOLFG, EPE), Rua Professor Lima Basto, 1099-023 Lisbon, Portugal"},{"name":"Familial Cancer Clinic, Instituto Portugu\u00eas de Oncologia de Lisboa Francisco Gentil E.P.E. (IPOLFG, EPE), Rua Professor Lima Basto, 1099-023 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isadora","family":"Rosa","sequence":"additional","affiliation":[{"name":"Gastroenterology Department, Instituto Portugu\u00eas de Oncologia de Lisboa Francisco Gentil E.P.E. (IPOLFG, EPE), Rua Professor Lima Basto, 1099-023 Lisbon, Portugal"},{"name":"Familial Cancer Clinic, Instituto Portugu\u00eas de Oncologia de Lisboa Francisco Gentil E.P.E. (IPOLFG, EPE), Rua Professor Lima Basto, 1099-023 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Familial Cancer Clinic, Instituto Portugu\u00eas de Oncologia de Lisboa Francisco Gentil E.P.E. (IPOLFG, EPE), Rua Professor Lima Basto, 1099-023 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4087-9940","authenticated-orcid":false,"given":"Ricardo","family":"Fonseca","sequence":"additional","affiliation":[{"name":"Pathology Department, Instituto Portugu\u00eas de Oncologia de Lisboa Francisco Gentil E.P.E. (IPOLFG, EPE), Rua Professor Lima Basto, 1099-023 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8388-4272","authenticated-orcid":false,"given":"Paula","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Familial Cancer Clinic, Instituto Portugu\u00eas de Oncologia de Lisboa Francisco Gentil E.P.E. (IPOLFG, EPE), Rua Professor Lima Basto, 1099-023 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joana","family":"Parreira","sequence":"additional","affiliation":[{"name":"Familial Cancer Clinic, Instituto Portugu\u00eas de Oncologia de Lisboa Francisco Gentil E.P.E. (IPOLFG, EPE), Rua Professor Lima Basto, 1099-023 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Claro","sequence":"additional","affiliation":[{"name":"Gastroenterology Department, Instituto Portugu\u00eas de Oncologia de Lisboa Francisco Gentil E.P.E. (IPOLFG, EPE), Rua Professor Lima Basto, 1099-023 Lisbon, Portugal"},{"name":"Familial Cancer Clinic, Instituto Portugu\u00eas de Oncologia de Lisboa Francisco Gentil E.P.E. (IPOLFG, EPE), Rua Professor Lima Basto, 1099-023 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9707-0317","authenticated-orcid":false,"given":"Cristina","family":"Albuquerque","sequence":"additional","affiliation":[{"name":"Molecular Pathobiology Research Unit (UIPM), Instituto Portugu\u00eas de Oncologia de Lisboa Francisco Gentil E.P.E. (IPOLFG, EPE), Rua Professor Lima Basto, 1099-023 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1053\/j.gastro.2019.11.310","article-title":"Update on the World Health Organization criteria for diagnosis of Serrated Polyposis Syndrome","volume":"158","author":"Dekker","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Guarinos, C., S\u00e1nchez-Fort\u00fan, C., Rodr\u00edguez-Soler, M., Alenda, C., Pay\u00e1, A., and Jover, R. Serrated polyposis syndrome: Molecular, pathological and clinical aspects. World J. Gastroenterol., 2012 18, 2452\u20132461.","DOI":"10.3748\/wjg.v18.i20.2452"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"101791","DOI":"10.1016\/j.bpg.2022.101791","article-title":"Serrated polyposis syndrome; epidemiology and management","volume":"58","author":"Carballal","year":"2022","journal-title":"Best Pract Res. Clin. Gastroenterol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1053\/j.gastro.2006.03.046","article-title":"Hyperplastic polyposis syndrome: Phenotypic presentations and the role of MBD4 and MYH","volume":"131","author":"Chow","year":"2006","journal-title":"Gastroenterology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2014","DOI":"10.1053\/j.gastro.2008.09.020","article-title":"Hyperplastic polyps and sessile serrated adenomas as a phenotypic expression of MYH-associated polyposis","volume":"135","author":"Boparai","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Clendenning, M., Young, J.P., Walsh, M.D., Woodall, S., Arnold, J., Jenkins, M., Win, A.K., Hopper, J.L., Sweet, K., and Gallinger, S. (2013). Germline mutations in the polyposis-associated genes BMPR1A, SMAD4, PTEN, MUTYH and GREM1 are not common in individuals with serrated polyposis syndrome. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0066705"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1053\/j.gastro.2013.10.045","article-title":"Germline mutations in oncogene-induced senescence pathways are associated with multiple sessile serrated adenomas","volume":"146","author":"Gala","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e00100","DOI":"10.14309\/ctg.0000000000000100","article-title":"Identification of a novel candidate gene for serrated polyposis syndrome germline predisposition by performing linkage analysis combined with whole-exome sequencing","volume":"10","author":"Toma","year":"2019","journal-title":"Clin. Transl. Gastroenterol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Soares de Lima, Y., Arnau-Collell, C., D\u00edaz-Gay, M., Bonjoch, L., Franch-Exp\u00f3sito, S., Mu\u00f1oz, J., Moreira, L., Oca\u00f1a, T., Cuatrecasas, M., and Herrera-Pariente, C. (2021). Germline and somatic whole-exome sequencing identifies new candidate genes involved in familial predisposition to serrated polyposis syndrome. Cancers, 13.","DOI":"10.3390\/cancers13040929"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Kokko, A., Laiho, P., Lehtonen, R., Korja, S., Carvajal-Carmona, L.G., J\u00e4rvinen, H., Mecklin, J.P., Eng, C., Schleutker, J., and Tomlinson, I.P. (2006). EPHB2 germline variants in patients with colorectal cancer or hyperplastic polyposis. BMC Cancer, 6.","DOI":"10.1186\/1471-2407-6-145"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"De Palma, F.D.E., D\u2019argenio, V., Pol, J., Kroemer, G., Maiuri, M.C., and Salvatore, F. (2019). The Molecular Hallmarks of the Serrated Pathway in Colorectal Cancer. Cancers, 11.","DOI":"10.3390\/cancers11071017"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1097\/DCR.0b013e3182a11cca","article-title":"Serrated polyposis: Colonic phenotype, extracolonic features, and familial risk in a large cohort","volume":"56","author":"Jasperson","year":"2013","journal-title":"Dis. Colon Rectum"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1136\/jmedgenet-2015-103298","article-title":"Inherited predisposition to colorectal cancer: Towards a more complete picture","volume":"52","author":"Short","year":"2015","journal-title":"J. Med. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"9828","DOI":"10.3748\/wjg.v20.i29.9828","article-title":"Genetic predisposition to colorectal cancer: Where we stand and future perspectives","volume":"20","author":"Valle","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1093\/jnci\/djj468","article-title":"Association of smoking, CpG island methylator phenotype, and V600E BRAF mutations in colon cancer","volume":"98","author":"Samowitz","year":"2006","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1038\/ajg.2009.757","article-title":"Hyperplastic polyposis syndrome is associated with cigarette smoking, which may be a modifiable risk factor","volume":"105","author":"Walker","year":"2010","journal-title":"Am. J. Gastroenterol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2310","DOI":"10.1158\/1055-9965.EPI-09-0211","article-title":"The association of lifestyle and dietary factors with the risk for serrated polyps of the colorectum","volume":"18","author":"Wallace","year":"2009","journal-title":"Cancer Epidemiol. Biomarkers Prev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1053\/j.gastro.2019.06.041","article-title":"Terminology, molecular features, epidemiology and management of serrated colorectal neoplasia","volume":"157","author":"Crockett","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"687","DOI":"10.3892\/ijmm.2016.2666","article-title":"Serrated polyposis associated with a family history of colorectal cancer and\/or polyps: The preferential location of polyps in the colon and rectum defines two molecular entities","volume":"38","author":"Silva","year":"2016","journal-title":"Int. J. Mol. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1158\/1940-6207.CAPR-20-0592","article-title":"Immune Responses Vary in Preinvasive Colorectal Lesions by Tumor Location and Histology","volume":"14","author":"Wallace","year":"2021","journal-title":"Cancer Prev. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1146\/annurev-genet-102108-134222","article-title":"How the fanconi anemia pathway guards the genome","volume":"43","author":"Moldovan","year":"2009","journal-title":"Annu. Rev. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.molcel.2010.09.019","article-title":"The DNA damage response: Making it safe to play with knives","volume":"40","author":"Ciccia","year":"2010","journal-title":"Mol. Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"543531","DOI":"10.4061\/2010\/543531","article-title":"DNA damage induced by alkylating agents and repair pathways","volume":"2010","author":"Kondo","year":"2010","journal-title":"J. Nucleic Acids"},{"key":"ref_24","first-page":"219","article-title":"Colorectal cancers choosing sides","volume":"1816","author":"Albuquerque","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_25","first-page":"147","article-title":"Tumorigenic bacteria in colorectal cancer: Mechanisms and treatments","volume":"19","author":"Li","year":"2021","journal-title":"Cancer Biol. Med."},{"key":"ref_26","first-page":"rs.3.rs-2458794","article-title":"Paneth cells as the origin of intestinal cancer in the context of inflammation","volume":"19","author":"Verhagen","year":"2023","journal-title":"Res. Sq."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1158\/1055-9965.EPI-19-1551","article-title":"A systematic literature review of whole exome and genome sequencing population studies of genetic susceptibility to cancer","volume":"29","author":"Rotunno","year":"2020","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1038\/ejhg.2016.44","article-title":"The Fanconi anemia DNA damage repair pathway in the spotlight for germile predisposition to colorectal cancer","volume":"24","author":"Carballal","year":"2016","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1111\/cup.13689","article-title":"Germline mutations predisposing to melanoma","volume":"47","author":"Toussi","year":"2020","journal-title":"J. Cutan. Pathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s13053-021-00189-8","article-title":"Expanding the phenotype of E318K (c.952G\u2009>\u2009A) MITF germline mutation carriers: Case series and review of the literature","volume":"19","author":"Oliveira","year":"2021","journal-title":"Hered. Cancer Clin. Pract."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Feliubadal\u00f3, L., Tonda, R., Gausachs, M., Trotta, J.R., Castellanos, E., L\u00f3pez-Doriga, A., Teul\u00e9, \u00c0., Tornero, E., Del Valle, J., and Gel, B. (2017). Benchmarking of whole exome sequencing and Ad Hoc designed panels for genetic testing of hereditary cancer. Sci. Rep., 7.","DOI":"10.1038\/srep37984"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"20","DOI":"10.12688\/wellcomeopenres.10069.1","article-title":"Accurate clinical detection of exon copy number variants in a targeted NGS panel using DECoN","volume":"1","author":"Fowler","year":"2016","journal-title":"Wellcome Open Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/21\/11848\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:26:12Z","timestamp":1760113572000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/21\/11848"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,4]]},"references-count":32,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["ijms252111848"],"URL":"https:\/\/doi.org\/10.3390\/ijms252111848","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,4]]}}}