{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T23:28:04Z","timestamp":1772321284432,"version":"3.50.1"},"reference-count":19,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,3,10]],"date-time":"2020-03-10T00:00:00Z","timestamp":1583798400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Approximately 10% of all breast cancer (BC) cases are familial and caused by inheritance of mutant BRCA1, BRCA2, or some other genes from the same DNA reparation pathway. Genetic counseling in families with cancer history is a powerful means for early cancer detection and active risk reduction through preventive interventions. This is the first report of the rare inherited BRCA2 frameshift-deletion mutation c.3847_3848delGT in one Lithuanian pedigree with the intense familial history of BC. Three BRCA2-positive blood relatives with BC of different biological types were identified in this pedigree with the same type mutation. All three cases were diagnosed with advanced stage ductal carcinoma. Markedly, polymorphic cells and numerous mitoses were identified in BC from the cases. Two patients from the family were diagnosed with the triple negative tumors, while one case had early onset of the hormone positive BC. Despite the variation in clinical and biological presentation of BC, all cases showed a good response to conventional treatment. In conclusion, the strong influence of BRCA2 mutation on the onset of BC of various biological types reveals the complexity of genetic counselling in families with BC history.<\/jats:p>","DOI":"10.3390\/medicina56030119","type":"journal-article","created":{"date-parts":[[2020,3,10]],"date-time":"2020-03-10T11:59:36Z","timestamp":1583841576000},"page":"119","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Recurrent Germline BRCA2 Gene Mutation in Lithuanian Family"],"prefix":"10.3390","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1953-040X","authenticated-orcid":false,"given":"Ieva","family":"Sadzevi\u010dien\u0117","sequence":"first","affiliation":[{"name":"Institute of Biosciences, Life Sciences Center, Vilnius University, Saul\u0117tekio Avenue 7, LT-10222 Vilnius, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olga","family":"Liaugaudien\u0117","sequence":"additional","affiliation":[{"name":"Department of Consultative Polyclinic, National Cancer Institute, Santari\u0161ki\u0173 1, LT-08406 Vilnius, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justinas","family":"Besusparis","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Vilnius University, \u010ciurlionio, 21 LT-03101 Vilnius, Lithuania"},{"name":"National Center of Pathology, Affiliate of Vilnius University Hospital Santaros Clinics, P. Baublio 5, LT-08406 Vilnius, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jolita","family":"Asadauskien\u0117","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, National Cancer Institute, Santari\u0161ki\u0173 1, LT-08406 Vilnius, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilona","family":"Kulikien\u0117","sequence":"additional","affiliation":[{"name":"Laboratory of Genetic Diagnostic, National Cancer Institute, Santari\u0161ki\u0173 1, LT-08406 Vilnius, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Birut\u0117","family":"Brasi\u016bnien\u0117","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, National Cancer Institute, Santari\u0161ki\u0173 1, LT-08406 Vilnius, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rasa","family":"Sabaliauskait\u0117","sequence":"additional","affiliation":[{"name":"Laboratory of Genetic Diagnostic, National Cancer Institute, Santari\u0161ki\u0173 1, LT-08406 Vilnius, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonata","family":"Jarmalait\u0117","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Oncology, National Cancer Institute, Santari\u0161ki\u0173 1, LT-08406 Vilnius, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e000361","DOI":"10.1136\/esmoopen-2018-000361","article-title":"Single-agent PARP inhibitors for the treatment of patients with BRCA-mutated HER2-negative metastatic breast cancer: A systematic review and meta-analysis","volume":"3","author":"Ceppi","year":"2018","journal-title":"ESMO Open"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Godet, I., and Gilkes, D.M. (2017). BRCA1 and BRCA2 mutations and treatment strategies for breast cancer. Integr. Cancer Sci. Ther., 4.","DOI":"10.15761\/ICST.1000228"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2539","DOI":"10.2147\/OTT.S102569","article-title":"Distinct implications of different BRCA mutations:efficacy of cytotoxic chemotherapy, PARP inhibition and clinical outcome in ovarian cancer","volume":"10","author":"Hollis","year":"2017","journal-title":"Onco Targ. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1007\/s10549-016-3777-0","article-title":"Toxity of (neo)adjuvant chemotherapy for BRCA1- and BRCA2- associated breast cancer","volume":"156","author":"Drooger","year":"2016","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1002\/humu.23406","article-title":"Mutational spectrum in a worldwide study of 29.700 families with BRCA1 or BRCA2 mutations","volume":"29","author":"Rebbeck","year":"2018","journal-title":"Hum. Mutat."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3093","DOI":"10.1002\/cncr.25911","article-title":"Clinical Outcome of Triple Negative Breast Cancer in BRCA1 Mutation Carriers and Non-carriers","volume":"117","author":"Lee","year":"2011","journal-title":"Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e2875","DOI":"10.1038\/cddis.2017.264","article-title":"Acquired cross-linker resistance associated with a novel spliced BRCA2 protein variant for molecular phenotyping of BRCA2 disruption","volume":"8","author":"Meyer","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1200\/JCO.2014.57.1414","article-title":"Inherited Mutations in 17 Breast Cancer Susceptibility Genes Among a Large Triple-Negative Breast Cancer Cohort Unselected for Family History of Breast Cancer","volume":"33","author":"Couch","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.1007\/s11033-011-0958-0","article-title":"Common BRCA1 and BRCA2 mutations in breast cancer families: A meta-analysis from systematic review","volume":"39","author":"Wang","year":"2012","journal-title":"Mol. Biol. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1007\/s10549-012-2006-8","article-title":"Recurrent germline mutations in BRCA1 and BRCA2 genes in high risk families in Israel","volume":"133","author":"Laitman","year":"2012","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s13053-016-0046-5","article-title":"Recurrent mutations of BRCA1, BRCA2 and PALB2 in the population of breast and ovarian cancer patients in Southern Poland","volume":"14","author":"Wojcik","year":"2016","journal-title":"Hered. Cancer Clin. Pract."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1111\/j.1399-0004.2009.01328.x","article-title":"Does family history predict the age at onset of new breast cancers in BRCA1 and BRCA2 mutation-positive families?","volume":"77","author":"Panchal","year":"2010","journal-title":"Clin. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1186\/1897-4287-2-3-131","article-title":"The pathology of hereditary breast cancer","volume":"2","author":"Honrado","year":"2004","journal-title":"Hered. Cancer Clin. Pract."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2335","DOI":"10.1002\/(SICI)1097-0142(19981201)83:11<2335::AID-CNCR13>3.0.CO;2-N","article-title":"The histologic phenotypes of breast carcinoma occurring before age 40 years in women with and without BRCA1 or BRCA2 germline mutations: A population-based study","volume":"83","author":"Armes","year":"1998","journal-title":"Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/bcr10","article-title":"The pathology of familial breast cancer: Morphological aspects","volume":"1","author":"Lakhani","year":"1999","journal-title":"Breast Cancer Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1023\/A:1005853022804","article-title":"Inherited BRCA2 mutation associated with high grade breast cancer","volume":"47","author":"Agnarsson","year":"1998","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"R122","DOI":"10.1186\/bcr3248","article-title":"Tumour morphology of early-onset breast cancers predicts breast cancer risk for first-degree relatives: The Australian Breast Cancer Family Registry","volume":"14","author":"Dite","year":"2012","journal-title":"Breast Cancer Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1093\/jnci\/90.15.1138","article-title":"Multifactorial analysis of differences between sporadic breast cancers and cancers involving BRCA1 and BRCA2 mutations","volume":"90","author":"Lakhani","year":"1998","journal-title":"J. Natl. Cancer Inst."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/56\/3\/119\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:05:52Z","timestamp":1760173552000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/56\/3\/119"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,10]]},"references-count":19,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,3]]}},"alternative-id":["medicina56030119"],"URL":"https:\/\/doi.org\/10.3390\/medicina56030119","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,10]]}}}