Somatic alterations in the genome are found in many human tumours. Chromosome rearrangements or base substitutions that activate cellular oncogenes appear to act dominantly. In contrast, recessive alleles apparently contribute to childhood retinoblastoma, as homozygosity (or hemizygosity ) for chromosome 13 is often established in tumours, by either mitotic nondisjunction or recombination. Parallels exist between retinoblastoma and childhood Wilms' tumour (WT). Retinoblastoma is often inherited and accompanied by a deletion of chromosome 13 (band q14), while WT is occasionally associated with aniridia and deletion of chromosome 11 band p13. Most Wilms' tumours are sporadic and not accompanied by these findings, although interstitial deletion of chromosome 11 in tumour, but not normal, cells has been reported. In view of these parallels, we compared constitutional and tumour DNAs from WT patients by using chromosome 11p DNA probes. We report here that although heterozygosity in constitutional DNAs was often preserved in tumour DNAs, one case developed homozygosity for chromosome 11p markers in tumour cells, implying the involvement of chromosomal events in revealing a recessive WT locus. This observation suggests the action of such general mechanisms in a tumour other than retinoblastoma.
We have investigated the cell types in mouse testis and ovary in which the c-mos protooncogene is normally transcribed. Blot hybridization analysis of electrophoretically fractionated RNAs from testes of mice with defects in germ-cell development and from prepubertal and adult mice indicated that c-mos was transcribed during male germ-cell development. Analysis of purified populations of spermatogenic cell types detected c-mos RNA in the earliest haploid postmeiotic germ cell, the round spermatid, indicating that c-mos was expressed transiently during spermatogenesis. c-mos RNA was detected by blot hybridization in the ovaries of prepubertal mice and decreased in relative concentration following gonadotropin-stimulated proliferation of granulosa cells. These results suggested that c-mos was transcribed in oocytes and were confirmed by detection of high levels of c-mos RNA in isolated grown oocytes. Thus, c-mos is expressed in both male and female germ cells, suggesting possible roles for this protooncogene in meiosis, germ-cell development, fertilization, and early embryogenesis.Cellular oncogenes have been identified by three approaches: (i) as homologs of retroviral oncogenes, (ii) as genes that induce transformation upon transfection of cultured cells, and (iii) as genes that are frequently altered in neoplasms by DNA rearrangement or amplification (see refs. 1-3 for reviews). Together, these approaches have identified 40-50 cellular genes that, as activated oncogenes, can induce at least some aspects of neoplastic transformation. The formation of activated oncogenes from their normal cellular homologs (termed protooncogenes) can occur as a consequence of changes in the regulation of gene expression, point mutations resulting in single amino acid substitutions, or DNA rearrangements resulting in the synthesis of recombinant fusion proteins from which portions of the normal amino acid sequence have been deleted.A physiologic role for normal cellular progenitors of four oncogenes, sis, erbB, fms and erbA, is indicated by their identification as the genes encoding platelet-derived growth factor, epidermal growth factor receptor, macrophage colony-stimulating factor receptor, and thyroid hormone receptor, respectively (4-9). However, normal functions of other protooncogenes remain obscure. While some protooncogenes are expressed in many types of proliferating cells, others display more restricted patterns of expression, suggesting that they may function in specific developmental pathways.An example of developmental regulation of a protooncogene is provided by the expression of high levels of a unique c-abl transcript during postmeiotic differentiation of male germ cells (10). A possible role for another protooncogene, c-mos, in reproductive processes is suggested by its specific transcription in testes and ovaries of adult mice (11). The testis and ovary contain specialized, hormonally responsive somatic cells, Sertoli and Leydig cells in the male and granulosa cells in the female, as well as germ cells (...
A transforming gene detected by transfection of chicken B-cell lymphoma DNA has been isolated by molecular cloning. It is homologous to a conserved family of sequences present in normal chicken and human DNAs but is not related to transforming genes of acutely transforming retroviruses. The nucleotide sequence of the cloned transforming gene suggests that it encodes a protein that is partially homologous to the amino terminus of transferrin and related proteins although only about one tenth the size of transferrin.
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