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Genomic profiles of a hepatoblastoma from a patient with Beckwith-Wiedemann syndrome with uniparental disomy on chromosome 11p15 and germline mutation of APC and PALB2

2017; Impact Journals LLC; Volume: 8; Issue: 54 Linguagem: Inglês

10.18632/oncotarget.20515

1949-2553

Shinn Young Kim, Seung‐Hyun Jung, Min Sung Kim, Mi-Ryung Han, Hyeon‐Chun Park, Eun Sun Jung, Sung Hak Lee, Sug Hyung Lee, Yeun‐Jun Chung,

Cancer-related gene regulation

// Shinn Young Kim 1, 4, 5, 6 , Seung-Hyun Jung 1, 2 , Min Sung Kim 2, 3 , Mi-Ryung Han 1, 4 , Hyeon-Chun Park 1, 4 , Eun Sun Jung 7 , Sung Hak Lee 7 , Sug Hyung Lee 1, 2, 3 and Yeun-Jun Chung 1, 4, 5 1 Department of Precision Medicine Research Center, College of Medicine, The Catholic University of Korea, Seoul, South Korea 2 Department of Cancer Evolution Research Center, College of Medicine, The Catholic University of Korea, Seoul, South Korea 3 Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, South Korea 4 Department of Integrated Research Center for Genome Polymorphism, College of Medicine, The Catholic University of Korea, Seoul, South Korea 5 Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, South Korea 6 Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, South Korea 7 Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul, South Korea Correspondence to: Yeun-Jun Chung, email: yejun@catholic.ac.kr Sug Hyung Lee, email: suhulee@catholic.ac.kr Keywords: hepatoblastoma, uniparental disomy, mutation, copy number alteration, BWS Received: May 30, 2017     Accepted: August 07, 2017     Published: August 24, 2017 ABSTRACT Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth disorder mainly associated with altered genomic imprinting at chromosome 11p15.5. Children with BWS, especially uniparental disomy (UPD) at 11p15.5, are at increased risk of embryonal tumors including hepatoblastoma. Although genetic alterations of sporadic hepatoblastomas have been identified, integrated germline and somatic alterations of BWS-related hepatoblastoma have not been reported. For this, we performed whole-exome sequencing and genome-wide loss of heterozygosity/copy number analyses using a single nucleotide polymorphism (SNP) array for a hepatoblastoma in a BWS infant with paternal UPD at chromosome 11p15.5. We found germline 11p15.5 UPD as well as germline mutations of APC and PALB2 in the patient. At the somatic level, we found a CTNNB1 hotspot mutation and chromosome 1q gain in the tumor. The development of hepatoblastoma in this case might be explained by predisposition of the germline events (11p15.5 UPD, mutations of APC and PALB2 ) and later by somatic events with CTNNB1 somatic mutation and 1q gain. To our knowledge, this is the first report of germline and somatic genomic alteration profiles in hepatoblastoma arising from BWS. Clinically, our results provide a rationale for performing a more strict and intense protocol for hepatoblastoma surveillance in a high-risk BWS infant, such as the UPD-carrying case, for early detection and treatment.