{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T07:58:43Z","timestamp":1776412723641,"version":"3.51.2"},"reference-count":34,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"8","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:sec>\n            <jats:title>PURPOSE<\/jats:title>\n            <jats:p>\n              Patients with germline pathogenic variants (PVs) in\n              <jats:italic>APC<\/jats:italic>\n              develop tens (attenuated familial adenomatous polyposis [AFAP]) to innumerable (classic FAP) adenomatous polyps in their colon and are at significantly increased lifetime risk of colorectal cancer. Up to 10% of FAP and up to 50% of patients with AFAP who have undergone DNA-only multigene panel testing (MGPT) do not have an identified PV in\n              <jats:italic>APC<\/jats:italic>\n              . We seek to demonstrate how the addition of RNA sequencing run concurrently with DNA can improve detection of germline PVs in individuals with a clinical presentation of AFAP\/FAP.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS<\/jats:title>\n            <jats:p>\n              We performed a retrospective query of individuals tested with paired DNA-RNA MGPT from 2021 to 2022 at a single laboratory and included those with a novel\n              <jats:italic>APC<\/jats:italic>\n              PV located in intronic regions infrequently covered by MGPT, a personal history of polyposis, and family medical history provided. All clinical data were deidentified in this institutional review board-exempt study.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS<\/jats:title>\n            <jats:p>\n              Three novel\n              <jats:italic>APC<\/jats:italic>\n              variants were identified in six families and were shown to cause aberrant splicing because of the creation of a deep intronic cryptic splice site that leads to an RNA transcript subject nonsense-mediated decay. Several carriers had previously undergone DNA-only genetic testing and had received a negative result.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSION<\/jats:title>\n            <jats:p>Here, we describe how paired DNA-RNA MGPT can be used to solve missing heritability in FAP families, which can have important implications in family planning and treatment decisions for patients and their families.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1200\/po.23.00404","type":"journal-article","created":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T19:59:20Z","timestamp":1712087960000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":6,"title":["Solving Missing Heritability in Patients With Familial Adenomatous Polyposis With DNA-RNA Paired Testing"],"prefix":"10.1200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9385-8262","authenticated-orcid":true,"given":"Colin C.","family":"Young","sequence":"first","affiliation":[{"name":"Ambry Genetics, Aliso Viejo, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5186-6208","authenticated-orcid":true,"given":"Carolyn","family":"Horton","sequence":"additional","affiliation":[{"name":"Ambry Genetics, Aliso Viejo, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3422-6441","authenticated-orcid":true,"given":"Jessica","family":"Grzybowski","sequence":"additional","affiliation":[{"name":"Ambry Genetics, Aliso Viejo, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nelly","family":"Abualkheir","sequence":"additional","affiliation":[{"name":"Ambry Genetics, Aliso Viejo, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jesus","family":"Ramirez Castano","sequence":"additional","affiliation":[{"name":"Ambry Genetics, Aliso Viejo, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bhuvan","family":"Molparia","sequence":"additional","affiliation":[{"name":"Ambry Genetics, Aliso Viejo, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5645-498X","authenticated-orcid":true,"given":"Rachid","family":"Karam","sequence":"additional","affiliation":[{"name":"Ambry Genetics, Aliso Viejo, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4082-371X","authenticated-orcid":true,"given":"Elizabeth","family":"Chao","sequence":"additional","affiliation":[{"name":"Ambry Genetics, Aliso Viejo, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4626-4920","authenticated-orcid":true,"given":"Marcy E.","family":"Richardson","sequence":"additional","affiliation":[{"name":"Ambry Genetics, Aliso Viejo, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"233","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1651563"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(81)90021-0"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2011-300348"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2006.00375.x"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-4-22"},{"key":"e_1_3_5_7_2","first-page":"95","article-title":"The genetic basis of familial adenomatous polyposis and its implications for clinical practice and risk management","volume":"8","author":"Leoz ML","year":"2015","unstructured":"Leoz ML, Carballal S, Moreira L, et al: The genetic basis of familial adenomatous polyposis and its implications for clinical practice and risk management. 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