{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T12:25:08Z","timestamp":1763036708941},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2012,7,4]],"date-time":"2012-07-04T00:00:00Z","timestamp":1341360000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"},{"start":{"date-parts":[[2012,7,4]],"date-time":"2012-07-04T00:00:00Z","timestamp":1341360000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Genome Med"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                        <jats:title>Background<\/jats:title>\n                        <jats:p>Recent advances in the treatment of cancer have focused on targeting genomicaberrations with selective therapeutic agents. In rare tumors, where large-scaleclinical trials are daunting, this targeted genomic approach offers a newperspective and hope for improved treatments. Cancers of the ampulla of Vater arerare tumors that comprise only about 0.2% of gastrointestinal cancers.Consequently, they are often treated as either distal common bile duct orpancreatic cancers.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>We analyzed DNA from a resected cancer of the ampulla of Vater and whole blood DNAfrom a 63 year-old man who underwent a pancreaticoduodenectomy by whole genomesequencing, achieving 37\u00d7 and 40\u00d7 coverage, respectively. We determinedsomatic mutations and structural alterations.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>We identified relevant aberrations, including deleterious mutations of <jats:italic>KRAS<\/jats:italic> and <jats:italic>SMAD4<\/jats:italic> as well as a homozygous focal deletion of the <jats:italic>PTEN<\/jats:italic> tumor suppressor gene. These findings suggest that these tumors have adistinct oncogenesis from either common bile duct cancer or pancreatic cancer.Furthermore, this combination of genomic aberrations suggests a therapeuticcontext for dual mTOR\/PI3K inhibition.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusions<\/jats:title>\n                        <jats:p>Whole genome sequencing can elucidate an oncogenic context and expose potentialtherapeutic vulnerabilities in rare cancers.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/gm357","type":"journal-article","created":{"date-parts":[[2012,7,5]],"date-time":"2012-07-05T05:08:55Z","timestamp":1341464935000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Cancer of the ampulla of Vater: analysis of the whole genome sequence exposes a potential therapeutic vulnerability"],"prefix":"10.1186","volume":"4","author":[{"given":"Michael J","family":"Demeure","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David W","family":"Craig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shripad","family":"Sinari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tracy M","family":"Moses","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexis","family":"Christoforides","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Dinh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tyler","family":"Izatt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Aldrich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ardis","family":"Decker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Baker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene","family":"Cherni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"April","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lawrence","family":"Koep","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas","family":"Lake","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Galen","family":"Hostetter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey M","family":"Trent","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel D","family":"Von Hoff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John D","family":"Carpten","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2012,7,4]]},"reference":[{"key":"379_CR1","doi-asserted-by":"publisher","first-page":"1273","DOI":"10.1056\/NEJMoa0908721","volume":"362","author":"J Valle","year":"2010","unstructured":"Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, Madhusudan S, Iveson T, Hughes S, Pereira SP, Roughton M, Bridgewater J: Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. 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