{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:44:40Z","timestamp":1791330280675,"version":"4.3.1"},"reference-count":25,"publisher":"National Academy of Sciences","issue":"16","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,4,17]]},"abstract":"<jats:p>\n                    No more than \u224830% of hereditary breast cancer has been accounted for by mutations in known genes. Most of these genes, such as\n                    <jats:italic>BRCA1<\/jats:italic>\n                    ,\n                    <jats:italic>BRCA2<\/jats:italic>\n                    ,\n                    <jats:italic>TP53<\/jats:italic>\n                    ,\n                    <jats:italic>CHEK2<\/jats:italic>\n                    ,\n                    <jats:italic>ATM<\/jats:italic>\n                    , and\n                    <jats:italic>FANCJ\/BRIP1<\/jats:italic>\n                    , function in DNA repair, raising the possibility that germ line mutations in other genes that contribute to this process also predispose to breast cancer. Given its close relationship with\n                    <jats:italic>BRCA2<\/jats:italic>\n                    ,\n                    <jats:italic>PALB2<\/jats:italic>\n                    was sequenced in affected probands from 68\n                    <jats:italic>BRCA1\/BRCA2<\/jats:italic>\n                    -negative breast cancer families of Ashkenazi Jewish, French Canadian, or mixed ethnic descent. The average BRCAPRO score was 0.58. A truncating mutation (229delT) was identified in one family with a strong history of breast cancer (seven breast cancers in three female mutation carriers). This mutation and its associated breast cancers were characterized with another recently reported but unstudied mutation (2521delA) that is also associated with a strong family history of breast cancer. There was no loss of heterozygosity in tumors with either mutation. Moreover, comparative genomic hybridization analysis showed major similarities to that of\n                    <jats:italic>BRCA2<\/jats:italic>\n                    tumors but with some notable differences, especially loss of 18q, a change that was previously unknown in\n                    <jats:italic>BRCA2<\/jats:italic>\n                    tumors and less common in sporadic breast cancer. This study supports recent observations that\n                    <jats:italic>PALB2<\/jats:italic>\n                    mutations are present, albeit not frequently, in breast cancer families. The apparently high penetrance noted in this study suggests that at least some\n                    <jats:italic>PALB2<\/jats:italic>\n                    mutations are associated with a substantially increased risk for the disease.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0701724104","type":"journal-article","created":{"date-parts":[[2007,4,9]],"date-time":"2007-04-09T20:59:07Z","timestamp":1176152347000},"page":"6788-6793","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":190,"title":["Analysis of\n                    <i>PALB2<\/i>\n                    \/\n                    <i>FANCN<\/i>\n                    -associated breast cancer families"],"prefix":"10.1073","volume":"104","author":[{"given":"Marc","family":"Tischkowitz","sequence":"first","affiliation":[{"name":"Program in Cancer Genetics, Departments of Oncology and Human Genetics and"},{"name":"Departments of Medicine and Human Genetics, McGill University, Montr\u00e9al, QC, Canada H2W 1S6;"},{"name":"Segal Cancer Centre and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Xia","sequence":"additional","affiliation":[{"name":"Dana\u2013Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelly","family":"Sabbaghian","sequence":"additional","affiliation":[{"name":"Program in Cancer Genetics, Departments of Oncology and Human Genetics and"},{"name":"Segal Cancer Centre and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge S.","family":"Reis-Filho","sequence":"additional","affiliation":[{"name":"The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, Fulham Road, London SW3 6JB, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Hamel","sequence":"additional","affiliation":[{"name":"Program in Cancer Genetics, Departments of Oncology and Human Genetics and"},{"name":"The Research Institute, McGill University Health Centre, Montr\u00e9al, QC, Canada H3G 1A4;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilan","family":"Li","sequence":"additional","affiliation":[{"name":"Dana\u2013Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik H.","family":"van Beers","sequence":"additional","affiliation":[{"name":"Division of Experimental Therapy and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Li","sequence":"additional","affiliation":[{"name":"Program in Cancer Genetics, Departments of Oncology and Human Genetics and"},{"name":"Segal Cancer Centre and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tayma","family":"Khalil","sequence":"additional","affiliation":[{"name":"Program in Cancer Genetics, Departments of Oncology and Human Genetics and"},{"name":"Departments of Medicine and Human Genetics, McGill University, Montr\u00e9al, QC, Canada H2W 1S6;"},{"name":"Segal Cancer Centre and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise A.","family":"Quenneville","sequence":"additional","affiliation":[{"name":"Department of Pathology, McGill University Sir M. B. Davis-Jewish General Hospital, 3755 C\u00f4te St-Catherine, Montr\u00e9al, QC, Canada H3T 1E2;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atilla","family":"Omeroglu","sequence":"additional","affiliation":[{"name":"Department of Pathology, McGill University, Montr\u00e9al, QC, Canada, H3A 2B4;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aletta","family":"Poll","sequence":"additional","affiliation":[{"name":"Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada M5G 1N9; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Lepage","sequence":"additional","affiliation":[{"name":"McGill University and Genome Qu\u00e9bec Innovation Centre, Montr\u00e9al, QC, Canada H3A 1A4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora","family":"Wong","sequence":"additional","affiliation":[{"name":"Program in Cancer Genetics, Departments of Oncology and Human Genetics and"},{"name":"Departments of Medicine and Human Genetics, McGill University, Montr\u00e9al, QC, Canada H2W 1S6;"},{"name":"Segal Cancer Centre and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra M.","family":"Nederlof","sequence":"additional","affiliation":[{"name":"Department of Pathology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Ashworth","sequence":"additional","affiliation":[{"name":"The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, Fulham Road, London SW3 6JB, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia N.","family":"Tonin","sequence":"additional","affiliation":[{"name":"Program in Cancer Genetics, Departments of Oncology and Human Genetics and"},{"name":"Departments of Medicine and Human Genetics, McGill University, Montr\u00e9al, QC, Canada H2W 1S6;"},{"name":"The Research Institute, McGill University Health Centre, Montr\u00e9al, QC, Canada H3G 1A4;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven A.","family":"Narod","sequence":"additional","affiliation":[{"name":"Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada M5G 1N9; 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