Document 0328
 DOCN  M9550328
 TI    Mutational hot spots within the carboxy terminal region of the LMP1
       oncogene of Epstein-Barr virus are frequent in lymphoproliferative
       disorders.
 DT    9505
 AU    Knecht H; Bachmann E; Brousset P; Rothenberger S; Einsele H; Lestou VS;
       Delsol G; Bachmann F; Ambros PF; Odermatt BF; Department of Internal
       Medicine, CHUV University Hospital,; Lausanne, Switzerland.
 SO    Oncogene. 1995 Feb 2;10(3):523-8. Unique Identifier : AIDSLINE
       MED/95148223
 AB    We have recently identified in Epstein-Barr virus (EBV) positive
       Hodgkin's disease (HD) a variant of the latent membrane protein 1 (LMP1)
       oncogene characterized by four point mutations and a 30 base pair
       deletion. These findings led us to test whether such mutants were also
       present in other lymphoproliferative disorders (LPD). We analysed 98 EBV
       DNA positive cases (67 LPD, 15 benign conditions, 16 lymphoblastoid cell
       lines) by PCR for deletions within the LMP1 gene. DNA sequencing of the
       region coding for the carboxy terminal protein domain was performed on
       24 cases. In 13 cases the same combination of 4 point mutations at
       positions 168,320, 168,308, 168,295 and 168,225 was identified. Of these
       cases, 12 had an additional point mutation at position 168,357 and eight
       at position 168,355, and nine had a 30 base pair deletion including
       nucleotides 168,285 to 168,256. These deletion mutants were identified
       in HD, angioimmunoblastic lymphadenopathy, B-immunoblastic lymphoma,
       peripheral T-cell lymphoma, and two lymphoblastoid cell lines. Our
       findings reveal a high frequency of non-random point mutations at
       preferential sites within the 3' (carboxy terminal) region of the LMP1
       oncogene. The association of these mutational hot spots with LPD
       suggests that they are involved in EBV related lymphomagenesis and that
       they define a clinically relevant EBV strain.
 DE    Antigens, Viral/*GENETICS  Arthritis, Rheumatoid/VIROLOGY  Base Sequence
       Cell Line  Cell Line, Transformed  Herpesvirus 4, Human/*GENETICS
       Hodgkin's Disease/VIROLOGY  Human  Lymphoproliferative
       Disorders/*VIROLOGY  Molecular Sequence Data  Oncogene Proteins,
       Viral/*GENETICS  Oncogenes/*GENETICS  Point Mutation  Sequence Deletion
       Support, Non-U.S. Gov't  Viral Matrix Proteins/*GENETICS  JOURNAL
       ARTICLE

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