title: Distinct set of chromosomal aberrations in childhood hepatocellular carcinoma is correlated to hepatitis B virus infection.
abstract: Hepatocellular carcinoma (HCC) is rarely observed in children and adolescents, but it is reported to be correlated with hepatitis B virus (HBV+) infections. This correlation is not easily explained, because in adults, HBV infections lead to the development of HCC only after decades, not within a few years. In HBV+ adulthood HCC, distinct chromosomal imbalances have been observed. Similar analyses have not been reported for childhood HCC. Here, we investigated whether chromosomal changes were associated with childhood HCC. We analysed formalin-fixed paraffin-embedded (FFPE) samples derived from 17 patients, 0-18 years old, who underwent partial hepatectomies due to HBV+ or HBV- associated HCC. In parallel, in 15 cases, we also analysed non-neoplastic liver tissues adjacent to the HCC. All samples were analysed with high resolution, microarray-based, comparative genomic hybridisation (aCGH). Overall, genomic aberrations in childhood HCC resembled those reported for adulthood HCC. In HBV+ HCC samples, chromosomes 1, 6, 7, 9, 17, 19, and 22 were significantly changed compared to those in HBV- HCC samples. Most interestingly, aberrations for chromosomes 7, 8, 9, 11, and 19 were also observed in corresponding non-neoplastic samples. A specific set of chromosomal abnormalities, including gains in chromosomes 8q, 9q, 11q, and 19, was significantly enriched in HBV+ compared to HBV- non-neoplastic tissues. In childhood HCC, HBV+ was correlated to increased chromosomal instability and specific chromosomal imbalances. A subset of aberrations might be essential in HCC carcinogenesis because they occurred in adjacent, non-neoplastic tissues. In particular, the gain in chromosome 19 appeared to be highly important.
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China; Institute of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China; Institute Pathology, University Bonn, Germany.
authors.forename: Lu
authors.initials: L
authors.lastname: Tan
authors.affiliation: Institute of Pathology, Nordstadtkrankenhaus (Klinikum Region Hannover), Hannover, Germany.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Meier
authors.affiliation: Institute of Pathology, Nordstadtkrankenhaus (Klinikum Region Hannover), Hannover, Germany.
authors.forename: Mareike
authors.initials: M
authors.lastname: Kuhlmann
authors.affiliation: Department of Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Xie
authors.affiliation: Institute of Pathology, Nordstadtkrankenhaus (Klinikum Region Hannover), Hannover, Germany.
authors.forename: Claas
authors.initials: C
authors.lastname: Baier
authors.affiliation: Institute of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Institute of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Wen-Ming
authors.initials: WM
authors.lastname: Cong
authors.affiliation: Institute of Pathology, Nordstadtkrankenhaus (Klinikum Region Hannover), Hannover, Germany; Institute of Human Genetics, Medical School Hannover, Germany. Electronic address: Ludwig.Wilkens@krh.eu.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Wilkens
mesh_terms: D000293:Adolescent; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D043171:Chromosomal Instability; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization; D005260:Female; D006509:Hepatitis B / Q000150:complications*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008113:Liver Neoplasms / Q000209:etiology / Q000235:genetics*; D008297:Male
keywords: HBV; HCC; aCGH; adjacent non-neoplastic tissues; children; chromosomal instability