title: SV40 and p53 as team players in childhood lymphoproliferative disorders.
abstract: Simian virus 40 (SV40) is known to be potently oncogenic and can induce several types of tumours, such as lymphoma. p53 was discovered as a cellular partner of the SV40 large T-antigen, the oncoprotein of this virus. There have not been many studies on SV40 and p53 in lymphomas and the ones that exist, are controversial. A comparison of these two components in lymphoma has not been reported previously. We examined 91 lymphomas [60 B-cell non-Hodgkin's lymphomas (B-NHLs), 19 B-cell acute lymphoblastic leukemias (B-ALLs), 7 B-cell precursor acute lymphoblastic leukemias and 5 T-cell acute lymphoblastic leukemias] for the presence of SV40. Overall, 40 samples from 12 B-NHL/19 B-ALL patients were additionally investigated for p53 mutation in the hot-spot exons 5 to 8. Overall, we found 62/91 lymphomas to be SV40-positive, among them 16/19 B-ALLs and 38/60 B-NHLs. SV40 was absent in 147 of the 149 blood control samples. We found 11 p53 mutations in 19 B-ALL patients: 5 in exon 5 (codons 132, 141, 143, 155 and 181), 4 in exon 7 (codons 236, 238 and 248), 2 in exon 8 (codon 273). In B-NHL patients we found p53-mutations in 9/12 samples: 6 of these in 3 lymph nodes (LNs). One LN harboured 3 different p53 mutations: Exon 5 (codon 132), exon 6 (codon 213) and exon 8 (codon 288). Another LN showed 2 different p53 mutations: Exon 6 (codon 213) and exon 8 (codon 285). Except for 1 nonsense mutation in an LN of a B-NHL patient, all 20 mutations were missense mutations, 2 were homozygous, both found in B-NHL-samples, and one of these (codon 175) is known to cause the global denaturation of p53. All occur in the DNA-binding domain of p53. All specimens showing a p53 mutation, were SV40-positive. p53 mutaions found in LNs of B-NHL patients harbour high SV40 copy numbers. Our data strongly support an important role for SV40, as well as a strong association of SV40 and p53 in childhood lympho-proliferative disorders.
authors.affiliation: University Medical Centre Hamburg Eppendorf, Centre for Women's and Children's Health, Clinic and Polyclinic for Paediatric Haematology and Oncology, Martinistr. 52, 20246 Hamburg, Germany. heinsohn@uke.uni-hamburg.de
authors.forename: Susanne
authors.initials: S
authors.lastname: Heinsohn
authors.forename: Roswitha
authors.initials: R
authors.lastname: Scholz
authors.forename: Hartmut
authors.initials: H
authors.lastname: Kabisch
mesh_terms: D000293:Adolescent; D000818:Animals; D019556:COS Cells; D002648:Child; D002675:Child, Preschool; D002522:Chlorocebus aethiops; D005091:Exons; D016158:Genes, p53 / Q000502:physiology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008232:Lymphoproliferative Disorders / Q000209:etiology* / Q000235:genetics / Q000821:virology; D009154:Mutation; D013539:Simian virus 40 / Q000302:isolation & purification*