{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T20:16:24Z","timestamp":1789676184661,"version":"4.0.1"},"reference-count":73,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"9","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>\n                      Pathogenic\/likely pathogenic variants (P\/LPVs) in the\n                      <jats:italic toggle=\"yes\">CDKN2A<\/jats:italic>\n                      gene cause an increased risk of melanoma (MEL) and pancreatic cancer (PANC). The\n                      <jats:italic toggle=\"yes\">CDKN2A<\/jats:italic>\n                      variant I49T (c.146T&gt;C), reported to be recurrent in Hispanics, has conflicting pathogenicity classifications at laboratories, affecting clinical care. Multiple genetics clinics collaborated to explore cancers associated with I49T.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Institutional clinical databases were queried for the\n                      <jats:italic toggle=\"yes\">CDKN2A<\/jats:italic>\n                      variants, I49T, known P\/LPVs, and c.-2G&gt;A (a benign variant [BV]), and history of PANC and MEL was abstracted. A combination of statistical tests was used to investigate cancer history associations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Data on 203 individuals, with qualifying\n                      <jats:italic toggle=\"yes\">CDKN2A<\/jats:italic>\n                      variants detected on multigene testing between 2012 and 2023, were analyzed (I49T, n = 101; known\n                      <jats:italic toggle=\"yes\">CDKN2A<\/jats:italic>\n                      P\/LPVs, n = 57; BV, n = 45). Those with I49T were 91% less likely to have MEL than known\n                      <jats:italic toggle=\"yes\">CDKN2A<\/jats:italic>\n                      P\/LPVs (odd ratio [OR] = 0.089 [95% CI, 0.031 to 0.025];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .001) and were also less likely to have PANC (OR = 0.45 [95% CI, 0.14 to 1.41];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .17). However, mean age at PANC diagnosis for I49T was 56.0 years, significantly younger than known\n                      <jats:italic toggle=\"yes\">CDKN2A<\/jats:italic>\n                      P\/LPVs (\u03bc = 71.0 years;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .026).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      In the largest I49T study to date to our knowledge, MEL was significantly less frequent compared with known\n                      <jats:italic toggle=\"yes\">CDKN2A<\/jats:italic>\n                      P\/LPVs. Although a nonsignificant trend was observed for less PANC in I49T than known P\/LPVs, individuals with I49T presented with PANC at a significantly younger age than those with known\n                      <jats:italic toggle=\"yes\">CDKN2A<\/jats:italic>\n                      P\/LPVs. The presence of I49T in Hispanics of mostly Mexican ancestry supports that it is a founder variant, relevant to understanding cancer risk in a large proportion of Hispanics in the United States.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/po-26-00083","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T19:59:13Z","timestamp":1789675153000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Exploring the Melanoma and Pancreatic Cancer Phenotype of a Potential\n                    <i>CDKN2A<\/i>\n                    Founder Variant, I49T (c.146T&gt;C; p.Ile49Thr), in Individuals of Predominantly Mexican Ancestry"],"prefix":"10.1200","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2473-5613","authenticated-orcid":true,"given":"Daisy","family":"Hernandez","sequence":"first","affiliation":[{"name":"Department of Medicine, Keck School of 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