{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:39:53Z","timestamp":1789000793645,"version":"build-2803163510"},"reference-count":51,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T00:00:00Z","timestamp":1720137600000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32071452"],"award-info":[{"award-number":["32071452"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81770173"],"award-info":[{"award-number":["81770173"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Germline mutations have been identified in a small number of hereditary cancers, but the genetic predisposition for many familial cancers remains to be elucidated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study identified a Chinese pedigree that presented different cancers (breast cancer, BRCA; adenocarcinoma of the esophagogastric junction, AEG; and B\u2010cell acute lymphoblastic leukemia, B\u2010ALL) in each of the three generations. Whole\u2010genome sequencing and whole\u2010exome sequencing were performed on peripheral blood or bone marrow and cancer biopsy samples. Whole\u2010genome bisulfite sequencing was conducted on the monozygotic twin brothers, one of whom developed B\u2010ALL.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>According to the ACMG guidelines, bioinformatic analysis of the genome sequencing revealed 20 germline mutations, particularly mutations in the DNAH11 (c.9463G\u2009&gt;\u2009A) and CFH (c.2314G\u2009&gt;\u2009A) genes that were documented in the COSMIC database and validated by Sanger sequencing. Forty\u2010one common somatic mutated genes were identified in the cancer samples, displaying the same type of single nucleotide substitution Signature 5. Meanwhile, hypomethylation of PLEK2, MRAS, and RXRA as well as hypermethylation of CpG island associated with WT1 was shown in the twin with B\u2010ALL.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings reveal genomic alterations in a pedigree with multiple cancers. Mutations found in the DNAH11, CFH genes, and other genes predispose to malignancies in this family. Dysregulated methylation of WT1, PLEK2, MRAS, and RXRA in the twin with B\u2010ALL increases cancer susceptibility. The similarity of the somatic genetic changes among the three cancers indicates a hereditary impact on the pedigree. These familial cancers with germline and somatic mutations, as well as epigenomic alterations, represent a common molecular basis for many multiple cancer pedigrees.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.7394","type":"journal-article","created":{"date-parts":[[2024,7,6]],"date-time":"2024-07-06T06:49:44Z","timestamp":1720248584000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Impact of genomic and epigenomic alterations of multigene on a multicancer pedigree"],"prefix":"10.1002","volume":"13","author":[{"given":"Jingyu","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Pediatrics Nanfang Hospital, Southern Medical University  Guangzhou China"},{"name":"Guangdong Provincial Key Laboratory of Single Cell Technology and Application Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7664-542X","authenticated-orcid":false,"given":"Yongzhang","family":"Wu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Single Cell Technology and Application Southern Medical University  Guangzhou China"},{"name":"Department of Biochemistry and Molecular Biology School of Basic Medical Sciences, Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieming","family":"Yu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Single Cell Technology and Application Southern Medical University  Guangzhou China"},{"name":"Affiliated Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5361-4781","authenticated-orcid":false,"given":"Yinbin","family":"Qiu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Single Cell Technology and Application Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiantian","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Nanfang Hospital, Southern Medical University  Guangzhou China"},{"name":"Guangdong Provincial Key Laboratory of Single Cell Technology and Application Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaochao","family":"Luo","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Single Cell Technology and Application Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junxiao","family":"Zhang","sequence":"additional","affiliation":[{"name":"SequMed Institute of Biomedical Sciences  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Fetal Medicine and Prenatal Diagnosis Zhujiang Hospital, Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Li","sequence":"additional","affiliation":[{"name":"Kaiser Permanente Regional Genetics Laboratory, San Jose Medical Center  San Jose California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fu","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics School of Basic Medical Sciences, Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuedong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Nanfang Hospital, Southern Medical University  Guangzhou China"},{"name":"Guangdong Provincial Key Laboratory of Single Cell Technology and Application Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinghua","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Nanfang Hospital, Southern Medical University  Guangzhou China"},{"name":"Guangdong Provincial Key Laboratory of Single Cell Technology and Application Southern Medical University  Guangzhou China"},{"name":"Department of Biochemistry and Molecular Biology School of Basic Medical Sciences, Southern Medical University  Guangzhou China"},{"name":"Precision Regenerative Medicine Research Centre, Division of Medical Sciences Macau University of Science and Technology  Macao China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,5]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13174385"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1235122"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10086"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13624-1"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2012.03.005"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-020-0638-4"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2054"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1207714"},{"issue":"3","key":"e_1_2_10_10_1","article-title":"Whole\u2010genome sequencing in cancer","volume":"9","author":"Zhao EY","year":"2019","journal-title":"Csh Perspect Med"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41698-021-00155-6"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12477"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abl9283"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200007133430201"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/PPO.0b013e31803c6e3b"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2017.01.020"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.2217\/epi.14.13"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-12-0095"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijgo.12997"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12881-019-0796-9"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-019-5494-7"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-18-0345"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2015.12.005"},{"issue":"3","key":"e_1_2_10_24_1","first-page":"269","article-title":"The transcription factor LSF: a novel oncogene for hepatocellular carcinoma","volume":"2","author":"Santhekadur PK","year":"2012","journal-title":"Am J Cancer Res"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12061653"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-10-1304"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.659049"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2022.11.023"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0034513"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-020-07183-8"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.7150\/jca.61385"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2013.07.102"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-019-1250-8"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/cac2.12349"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41594-022-00841-4"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jncc.2022.02.002"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13053-023-00247-3"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.03.039"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1508054"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16293-7"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2018.09.002"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/0168-9525(93)90209-Z"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-1932"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4419-9967-2_2"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21765"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.21123"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15133491"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgp220"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3934"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4292"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-1943-3"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-022-00509-4"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.7394","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T13:32:56Z","timestamp":1721914376000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.7394"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7]]},"references-count":51,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2024,7]]}},"alternative-id":["10.1002\/cam4.7394"],"URL":"https:\/\/doi.org\/10.1002\/cam4.7394","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7]]},"assertion":[{"value":"2024-01-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e7394"}}