Based on the capacity to transfer a-L-fucose onto type-1 and type-2 synthetic blood group H and sialylated acceptors, a comparison of the a-3-fucosyltransferase activities of different human tissues is shown. Three distinct acceptor specificity patterns are described: (I) myeloid a-3-fucosyltransferase pattern, in which leukocytes and brain enzymes transfer fucose actively onto H type-2 acceptor and poorly onto sialylated N-acetyllactosamine; (11) plasma a-3-fucosyltransferase (EC 2.4.1.152), in which plasma and hepatocyte enzymes transfer, in addition, onto the sialylated N-acetyllactosamine; (111) Lewis a-3/4-fucosyltransferase (EC 2.4.1.65), in which gall-bladder, kidney and milk enzymes transfer, in addition, onto type-1 acceptors. The small amount (< 10%) of a-3-fucosyltransferase activity found in the plasma of an a-3-fucosyltransferase-deficient individual had a myeloidtype acceptor pattern, suggesting that this small proportion of the plasma enzyme is derived from leukocytes. In addition to the three acceptor specificity patterns, these enzyme activities can be differentiated by their optimum pH: 8.0-8.7 for the enzymes from myeloid cells and brain, 7.2-8.0 for liver enzymes and 6.0-7.2 for gallbladder enzymes. Milk samples had two a-3-fucosyltransferase activities, the Lewis or a-3/4-fucosyltransferase under control of the Lewis gene and an a-3-fucosyltransferase with plasma acceptor pattern which was independent of the control of the Lewis gene. The apparent affinity for GDP-fucose of the myeloid-like enzyme was weaker than those of the plasma and Lewis-like enzymes. The apparent affinities for H type 2 and sialylated Nacetyllactosamine were stronger for exocrine secretions as compared to the plasma and myeloid enzymes. The plasma type of a-3-fucosyltransferase activity was more sensitive to N-ethylmaleimide and heat inactivation than the samples with myeloid-like a-3-fucosyltransferase activity.The names X, Le", SSEA-1 and CD15 have been used to describe different properties of the same epitope, the terminal trisaccharide 3-fucosyl-N-acetyllactosamine or Galjl-+ 4(Fucal --f 3)GlcNAcP-, which is found in 0-and N-linked glycoproteins and in glycolipids [I].Many monoclonal antibodies, raised against different cells, were shown to react specifically with this epitope [2, 31. The first monoclonal with this specificity [4] was called SSEA-1 (stage-specific embryonic antigen-1) because it reacted with 8-cell-stage mouse embryos, morulae and early blastocysts. However, monoclonal antibodies reacting with normal human granulocytes [5], myeloid cell lines [6], human neuroblastoma, fetal brain [7], human gastric, colon and lung cancers [8] also had the same trisaccharide specificity.The epitope at the cell surface of leukocytes has been termed CD15 (cluster of differentiation 15) because a group of monoclonal antibodies with this specificity was identified

Accumulation of extrachromosomal DNA molecules (double minute) is often responsible for gene amplification in cancers, but the mechanisms leading to their formation are still largely unknown. By using quantitative PCR, chromosome walking, in situ hybridization on metaphase chromosomes and whole genome analysis, we studied a glioma containing four extrachromosomally amplified loci (7p11, 1q32.1, 5p15 and 9p2). Complex extrachromosomal DNA molecules were formed by the fusion of several syntenic or non-syntenic DNA fragments from 7p11, 5p15 to 9p2. Fragments ranged from a few base pairs to megabase pairs. Scars of the amplification process remained at the original locus in the form of deletions or chromosome rearrangements. Chromosome fragmentation, due to replication stress, could explain this complex situation. In contrast, at 1q32.1, the initial extrachromosomal DNA molecule resulted from the circularization of a single fragment associated with an intrachromosomal deletion including, but larger than, the amplified sequence. The nature of the sequences involved in these rearrangements suggests that a V(D)J-like illegitimate recombination contributes to its formation.

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The mutagenic properties of ionizing radiation are well known, but the presence of specific mutations in human radiation-induced tumours is not established. We have studied a series of 36 secondary sarcomas arising in the irradiation field of a primary tumour following radiotherapy. The allelic status and the presence of mutations of the TP53 gene were investigated. The mutation pattern was compared with data from sporadic sarcomas recorded in the IARC TP53 somatic mutations database. A high proportion (58%) of the radiation-induced sarcomas exhibited a somatic inactivating mutation for one allele of TP53, systematically associated with a loss of the other allele. The high frequency (52%) of short deletions observed in the mutation pattern of radiation-induced sarcomas may be related to the induction of DNA breaks by ionizing radiation. The lack of hyper-reactivity of CpG dinucleotides and the presence of recurrent sites of mutation at codons 135 and 237 seem also to be specific for radiation tumorigenesis.