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
Metrics: PDF 1487 views | HTML 1941 views | ?
Shinn Young Kim1,4,5,6, Seung-Hyun Jung1,2, Min Sung Kim2,3, Mi-Ryung Han1,4, Hyeon-Chun Park1,4, Eun Sun Jung7, Sung Hak Lee7, Sug Hyung Lee1,2,3 and Yeun-Jun Chung1,4,5
1Department of Precision Medicine Research Center, College of Medicine, The Catholic University of Korea, Seoul, South Korea
2Department of Cancer Evolution Research Center, College of Medicine, The Catholic University of Korea, Seoul, South Korea
3Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, South Korea
4Department of Integrated Research Center for Genome Polymorphism, College of Medicine, The Catholic University of Korea, Seoul, South Korea
5Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, South Korea
6Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, South Korea
7Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul, South Korea
Yeun-Jun Chung, email: [email protected]
Sug Hyung Lee, email: [email protected]
Keywords: hepatoblastoma, uniparental disomy, mutation, copy number alteration, BWS
Received: May 30, 2017 Accepted: August 07, 2017 Published: August 24, 2017
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.