Consistent cytogenetic aberrations in hepatoblastoma: A common pathway of genetic alterations in embryonal liver and skeletal muscle malignancies?

Abstract

Cytogenetic analyses of four consecutive hepatoblastomas revealed near-diploid stemline karyotypes with relatively simple chromosome aberrations. Cytogenetic abnormalities shared by each tumor included trisomy for all of part of chromosome 2 and trisomy for chromosome 20. In two cases, partial trisomy for chromosome 2 resulted from direct duplication of long arm material with the shortest region of overlap being 2q23-2q35. In one tumor, each metaphase also contained a variable number of double minute chromosomes found not to derive from NMYC amplification. Interestingly, trisomy for 2q and trisomy 20 are also characteristic events in pediatric embryonal rhabdomyosarcomas. Furthermore, others have reported loss of heterozygosity for the short arm of chromosome 11 in both hepatoblastoma and childhood embryonal rhabdomyosarcoma, and both these malignant diseases are associated with Beckwith-Wiedemann syndrome. These cytogenetic and molecular findings suggest a parallel pathway of genetic steps in the initiation and/or progression of tumors of embryonal liver and skeletal muscle.

Cytogenetics of hepatoblastoma: Further characterization of 1q rearrangements by fluorescence in situ hybridization: An international collaborative study

“…Similar 1q imbalances have also been described, often as secondary changes, in other pediatric neoplastic disorders, such as acute lymphoblastic leukemia, retinoblastoma, Wilms tumor, and Ewing sarcoma, indicating that these aberrations are related to tumor progression [30,31]. Because of the frequent involvement of 1q12 and 1q21 in HBT [19,22,24,28] (also, the present investigation], FISH analyses were performed to try to map the breakpoints more precisely. Among the four cases analyzed, two were informative as regards 1q abnormalities, and both were found to display pericentromeric breakpoints.…”

“…Several previous cytogenetic studies have shown frequent structural as well as numerical abnormalities of chromosome 8 in HBT, often resulting in gain of 8q and loss of 8p [5,19,[21][22][23][24][25][26][27][28][29], but, again, these changes are not specific for HBT. On the contrary, similar chromosome 8 aberrations have been reported in a wide variety of neoplastic disorders [14], suggesting that these imbalances are of general importance in tumor development.…”

Comparative genomic hybridization analysis of hepatoblastomas

“…However, the majority of patients with hepatoblastoma do not have either syndrome. To our knowledge, cytogenetic analysis has been reported in only 21 confirmed hepatoblastomas in the pediatric age group (Petkovic et al, 1985;Mascarello et al, 1990;Bardi et al, 1991Bardi et al, , 1992Fletcher et al, 1991;Soukup et al, 1991;Anneren et al, 1992;Tonk et al, 1994;Swarts et al, 1996;Schneider et al, 1997). These studies have demonstrated that the most common recurring abnormalities are trisomies for chromosomes 2 and 20, and a recurrent translocation involving chromosomes 1 and 4 has been identified in a minority of cases.…”

Analysis of CDKN2A, CDKN2B, CDKN2C, and cyclin Ds gene status in hepatoblastoma

“…[36][37] Trisomy of chromosomes 2 and 8 and aberrations at the long arm of chromosome 1 (around 1q21) have also been shown in several cases of hepatoblastomas. [38][39][40][41] However, these karyotypic findings shed scarce light on the putative oncogenes or tumor suppressor genes involved in hepatoblastoma development and progression.…”