Cytogenetic findings in pediatric adipose tumors: consistent rearrangement of chromosome 8 in lipoblastoma.
ABSTRACT Characteristic cytogenetic aberrations have been reported in adult lipomas and liposarcomas, but few karyotypes have been reported for pediatric adipose neoplasms. In this report we describe a consistent rearrangement, der(8)(pter-->q13::q24.1-->qter), in 2 of 3 lipoblastomas. A similar der(8) was present in the only other published lipoblastoma karyotype, but this der(8) has not been reported in lipomas, liposarcomas, or nonadipose solid tumors. We investigated the potential specificity of der(8)(pter-->q13::q24.1-->qter) by karyotyping an unselected series of nonlipoblastoma adipose tumors in children and young adults. The series included 14 lipomas, 2 atypical lipomas ("well-differentiated liposarcomas"), and 2 angiomyolipomas; der(8) was not found in any tumor from this series. Three lipomas, however, contained rearrangements in the region of chromosome band 12q14, as has been described frequently in adult lipomas. Because clinical features in lipoblastoma can mimic those in liposarcoma, recognition of der(8)(pter-->q13::q24.1--qter) is of potential diagnostic relevance.
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ABSTRACT: Lipoblastomas are rare soft tissue tumors that occur primarily in young children. They typically contain variably differentiated adipocytes, primitive mesen- chymal cells, myxoid matrix, and fibrous trabeculae. Abnormalities in chromosome 8, leading to rear- rangements of the PLAG1 gene, were demonstrated recently in four lipoblastomas. In the present report, we determine the frequency of PLAG1 alterations in 16 lipoblastomas from children aged 13 years or younger, and we also evaluate the stages of lipoblas- toma differentiation at which PLAG1 genomic alter- ations are found. Eleven lipoblastomas (69%), includ- ing those with either classic or lipoma-like histology, had rearrangements of the 8q12 PLAG1 region. An- other three lipoblastomas had polysomy for chromo- some 8 in the absence of PLAG1 rearrangement. Only two cases (13%) lacked a chromosome 8 abnormality. Notably, the lipoblastomas with chromosome 8 poly- somy had up to five copies of chromosome 8 as an isolated cytogenetic finding in an otherwise diploid cell. We also demonstrate that PLAG1 alterations are found in a spectrum of mesenchymal cell types in lipoblastomas, including lipoblasts, mature adipo- cytes, primitive mesenchymal cells, and fibroblast- like cells. This finding is consistent with neoplastic origin in a primitive mesenchymal precursor and with variable differentiation to a mature adipocyte end-point. Hence, our studies provide biological val- idation for the clinical observation that lipoblastomas can evolve into mature, lipoma-like, lesions. They also suggest that PLAG1 dosage alterations caused by polysomy 8 might represent an alternative oncogenic mechanism in lipoblastoma. (Am J Pathol 2001, 159:955-962)
Article: [Congenital tumors].[Show abstract] [Hide abstract]
ABSTRACT: Tumors presenting in the newborn period are rare, although pathologists working at busy obstetric or neonatal units can expect to see occasional cases (Isaacs 1997, 2002b). The incidence is around 1 in 12,000 to 1 in 27,500 live births (Moore et al. 2003). Many of these tumors are specifi c to infants or behave differently from their counterparts in older children. Lack of familiarity with neonatal tumors may lead to unnecessarily aggressive therapy or well-intentioned neglect. Some neonatal tumors may appear to be aggressive lesions and yet be benign and, conversely, others look benign but may be fatal if incompletely excised. Most, but not all, childhood neoplasms have been described in the perinatal period. As in children generally, they are often mesenchymal rather than epithelial in his-togenesis, and knowledge of normal human development is often useful. Space limitations prevent this chapter from being comprehensive, so the focus is on the special characteristics of neonatal tumors that infl uence their diagnosis and management, and this chapter also discusses some areas where the study of neonatal tumors is of interest to our understanding of neoplasia in general. Some characteristic lesions not mentioned elsewhere in the text are listed in Table 15.1. Isaacs (1997, 2002; Las Heras and Isaacs 1987) in particular has presented extensive reviews of the subject. Neonatal tumors accounted for 2.6% of all children's tumors in his series, of which 40% were malignant. About 40% of malignant tumors in neonates are evident on the fi rst day of life, and 17% only discovered at autopsy (Campbell et al. 1987). Most malignant congenital tumors present in the fi rst week. A congenital tumor is one that is present at birth, but it is reasonable to suppose that any tumor presenting in the fi rst 3 months of life is congenital. It is now becoming clear that other childhood tumors, including many leukemias, Wilms' tumors, bronchopulmonary blastomas, and neuroblastomas, appear to arise from cells or lesions that are already abnormal at the time of birth. Children who present with acute leukemia can be found to have identical genetic changes in their leukemia and in the DNA from their Guthrie card or in the leukemia in their monozygotic twin (Greaves 2005). More neonates have these genetic changes than do children who develop leukemia. These studies show that many childhood leuke-mias have precursor cells that have undertaken the initial genetic steps of neoplastic progression at birth, although they do not necessarily progress to malignancy, a situation well described with nephrogenic rests and Wilms' tumors. This then raises the question of why tumors in infants are different from those in adults, which may be partly explained by the time needed for mutations to develop in epithelial tissues for adult tumors to occur and for exposure to mutagenic environmental agents. In other cases, such as Wilms' tumors, the cell of origin is probably the meta-nephric blastema that regresses during development. However, for acute leukemia, for example, the stem cells persist through life and the reasons are less clear but probably relate to the fetal environment and development.Pediatrics and Related Topics 02/1973; 12(6):377-96. DOI:10.1007/978-1-84628-743-5_15
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ABSTRACT: We have karyotyped eight sporadic osteocartilaginous exostoses (OCE), a tumor type not characterized cytogenetically before. Five tumors had only normal karyotypes, whereas three displayed the following abnormal karyotypes: 46,XY,del(8)(q24.1); 46,XX,del(8)(q22), t(8;14)(q24.1;q32); and 46,XY,der(8)t(1;8)(q21;q24),inv(12)(p11q13). All three aberrant cases thus had structural rearrangements leading to loss of the distal part of 8q. This is of particular interest because multiple OCE are part of the disease phenotype in patients with the autosomal dominant tricho-rhino-phalangeal syndrome type II (TRP II), many of whom have constitutional loss of genetic material from 8q24.1. We hypothesis that band 8q24.1 harbors a tumor suppressor gene, the homozygous inactivation of which is important in the genesis of both inherited and sporadic OCE. In the familial form, i.e., in TRP II, loss or functional inactivation of one allele is inherited and only the second mutation is due to a somatic event, whereas both mutations are somatic in the sporadic forms. This hypothesis can be tested by analysis of sporadic and inherited OCE for homozygous loss of 8q24 material with molecular genetic techniques.Genes Chromosomes and Cancer 01/1994; 9(1):8-12. DOI:10.1002/gcc.2870090103 · 3.84 Impact Factor