{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:13:07Z","timestamp":1787026387133,"version":"build-2736575974"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,11,7]],"date-time":"2022-11-07T00:00:00Z","timestamp":1667779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>\n                    Genetic testing has become the standard of care for many disease states. As a result, physicians treating patients who have tumors often rely on germline genetic testing results for making clinical decisions. Cases of two sisters carrying a germline\n                    <jats:italic>CHEK2<\/jats:italic>\n                    variant are highlighted whereby possible other genetic drivers were discovered on tumor analysis\n                    <jats:italic>. CHEK2<\/jats:italic>\n                    (also referred to as CHK2) loss of function has been firmly associated with breast cancer development. In this case report, two siblings with a germline\n                    <jats:italic>CHEK2<\/jats:italic>\n                    mutation also had distinct endocrine tumors. Pituitary adenoma and pancreatic neuroendocrine tumor (PNET) was found in the first sibling and pheochromocytoma (PCC) discovered in the second sibling. Although pituitary adenomas, PNETs, and PCC have been associated with\n                    <jats:italic>NF1<\/jats:italic>\n                    gene mutations, the second sister with a PCC did have proven germline\n                    <jats:italic>CHEK2<\/jats:italic>\n                    with a pathogenic somatic\n                    <jats:italic>NF1<\/jats:italic>\n                    mutation. We highlight the clinical point that unless the tumor is sequenced, the real driver mutation that is causing the patient\u2019s tumor may remain unknown.\n                  <\/jats:p>","DOI":"10.3389\/fendo.2022.1024108","type":"journal-article","created":{"date-parts":[[2022,11,7]],"date-time":"2022-11-07T02:20:11Z","timestamp":1667787611000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Case report: Two sisters with a germline CHEK2 variant and distinct endocrine neoplasias"],"prefix":"10.3389","volume":"13","author":[{"given":"Raphaelle D.","family":"Vallera","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanli","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimmo J.","family":"Hatanpaa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin A.","family":"Bishop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sasan","family":"Mirfakhraee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdel A.","family":"Alli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergei G.","family":"Tevosian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mouna","family":"Tabebi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Gimm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"S\u00f6derkvist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Estrada-Zuniga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia L. M.","family":"Dahia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans K.","family":"Ghayee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,11,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1086\/341943","article-title":"A CHEK2 genetic variant contributing to a substantial fraction of familial breast cancer","volume":"71","author":"Vahteristo","year":"2002","journal-title":"Am J Hum Genet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/ng879","article-title":"Low-penetrance susceptibility to breast cancer due to CHEK2(*)1100delC in noncarriers of BRCA1 or BRCA2 mutations","volume":"31","author":"Meijers-Heijboer","year":"2002","journal-title":"Nat Genet"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.2147\/BCTT.S111394","article-title":"Current perspectives on CHEK2 mutations in breast cancer","volume":"9","author":"Apostolou","year":"2017","journal-title":"Breast Cancer"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2018.1986","article-title":"Prevalence of germline mutations in cancer susceptibility genes in patients with advanced renal cell carcinoma","volume":"4","author":"Carlo","year":"2018","journal-title":"JAMA Oncol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1101\/gad.14.3.278","article-title":"Chk2\/hCds1 functions as a DNA damage checkpoint in G(1) by stabilizing p53","volume":"14","author":"Chehab","year":"2000","journal-title":"Genes Dev"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1210\/js.2018-00343","article-title":"Case report of an adrenocortical carcinoma associated with germline CHEK2 mutation","volume":"3","author":"Xie","year":"2019","journal-title":"J Endocrine Soc"},{"key":"B7","doi-asserted-by":"publisher","first-page":"4397","DOI":"10.3390\/ijerph17124397","article-title":"CHEK2 mutation in patient with multiple endocrine glands tumors. case report","volume":"17","author":"Szeliga","year":"2020","journal-title":"Int J Environ Res Public Health"},{"key":"B8","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1038\/nature21063","article-title":"Whole-genome landscape of pancreatic neuroendocrine tumours","volume":"543","author":"Scarpa","year":"2017","journal-title":"Nature"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1159\/000513679","article-title":"The CHEK2*1100delC mutation and adolescent breast cancer: A case report of breast cancer in a 19-Year-Old and a review of the literature","volume":"17","author":"Soleimani","year":"2022","journal-title":"Breast Care (Basel)"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1093\/labmed\/lmz009","article-title":"Prognostic significance of CHEK2 mutation in progression of breast cancer","volume":"50","author":"Ansari","year":"2019","journal-title":"Lab Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90408-5","article-title":"Somatic mutations in the neurofibromatosis 1 gene in human tumors","volume":"69","author":"Li","year":"1992","journal-title":"Cell"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.1180","article-title":"Expanding the noonan spectrum\/RASopathy NGS panel: Benefits of adding NF1 and SPRED1","volume":"8","author":"Witkowski","year":"2020","journal-title":"Mol Genet Genomic Med"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1186\/1479-7364-5-6-623","article-title":"Neurofibromatosis type 1-associated tumours: their somatic mutational spectrum and pathogenesis","volume":"5","author":"Laycock-van Spyk","year":"2011","journal-title":"Hum Genomics"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3648","article-title":"Pheochromocytoma and paraganglioma pathogenesis: learning from genetic heterogeneity","volume":"14","author":"Dahia","year":"2014","journal-title":"Nat Rev Cancer"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc066006","article-title":"Clinical and genetic characteristics of patients with neurofibromatosis type 1 and pheochromocytoma","volume":"354","author":"Bausch","year":"2006","journal-title":"N Engl J Med"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1097\/MED.0000000000000634","article-title":"Genetics of pheochromocytoma and paraganglioma","volume":"28","author":"Wachtel","year":"2021","journal-title":"Curr Opin Endocrinol Diabetes Obes"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2010-0181","article-title":"Neoplasms associated with germline and somatic NF1 gene mutations","volume":"17","author":"Patil","year":"2012","journal-title":"Oncologist"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds374","article-title":"Somatic NF1 inactivation is a frequent event in sporadic pheochromocytoma","volume":"21","author":"Burnichon","year":"2012","journal-title":"Hum Mol Genet"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds402","article-title":"Integrative genomics reveals frequent somatic NF1 mutations in sporadic pheochromocytomas","volume":"21","author":"Welander","year":"2012","journal-title":"Hum Mol Genet"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0065624","article-title":"Progenitor cell line (hPheo1) derived from a human pheochromocytoma tumor","volume":"8","author":"Ghayee","year":"2013","journal-title":"PloS One"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2017-01991","article-title":"Pheochromocytoma\/Paraganglioma: A poster child for cancer metabolism","volume":"103","author":"Tevosian","year":"2018","journal-title":"J Clin Endocrinol Metab"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdv022","article-title":"Genetics of breast cancer: a topic in evolution","volume":"26","author":"Shiovitz","year":"2015","journal-title":"Ann Oncol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1007\/978-3-030-20301-6_2","article-title":"Epidemiology of breast cancer in women","volume":"1152","author":"Coughlin","year":"2019","journal-title":"Adv Exp Med Biol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"8072","DOI":"10.3390\/ijms21218072","article-title":"Activation of RAS signalling is associated with altered cell adhesion in phaeochromocytoma","volume":"21","author":"Rossitti","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-019-0572-y","article-title":"Identification of cancer driver genes based on nucleotide context","volume":"52","author":"Dietlein","year":"2020","journal-title":"Nat Genet"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000010894","article-title":"Germline mutation of CHEK2 in neurofibromatosis 1 and 2: Two case reports","volume":"97","author":"Li","year":"2018","journal-title":"Med (Baltimore)"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.1024108\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T07:11:04Z","timestamp":1667977864000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.1024108\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,7]]},"references-count":26,"alternative-id":["10.3389\/fendo.2022.1024108"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2022.1024108","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.742451071.793597098","asserted-by":"object"}]},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,7]]},"article-number":"1024108"}}