Molecular Genetic Analysis of Intravascular Malignant Lymphomatosis (IML)

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Intravascular malignant lymphomatosis (IML) is a disease characterized by proliferation of neoplastic cells within small vessels in many organs, especially in the brain. The origin of these cells has long been discussed. Recently, immunohistochemical studies and Southern blot analyzes have suggested that these neoplastic cells were of lymphocytic nature. However, the genetic characteristics of the neoplastic cells including their antigen receptor genes and tumor suppressor genes have not yet been fully detailed. In this study, we examined the complementarity-determining region III (CDR-III) of rearranged immunoglobulin heavy chain (IgH) genes, first. CDR III sequences were amplified using the polymerase chain reaction (PCR) and consensus primers for the Variable and Joining regions of the IgH gene. PCR products were examined by polyacrylamide gel electrophoresis. Specimens from B cell lymphomas including IML produced a monoclonal band ; monoclonality was specific for this disorder. Spe … More cimens from peripheral blood cells produced a broad smear of polyclonal material ; and specimens from metastatic carcinomas and brain tumors produced either no amplification or polyclonal material. By cloning and sequencing the amplified CDR III,we have determined nucleotide sequences of rearranged regions of immunoglobulin genes in IML cases. This strafegy should be useful for detecting neoplastic cells in IML at an early stage (manuscript in preparation) . In this study, we also examined tumor suppressor genes in IML.The polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis revealed no abnormal migration in exons 5 to 8 of the p53 gene and exon 2 of the p16 (MTSI) gene. These findings suggested that mutation of p53 and p16 genes is rarely related with the tumorigenesis of IML.In PCR-SSCP analysis for exon 2 of the p21 (WAF1) , aberrant bands were seen in all of IML cases. By subsequent and sequencing, a nucleotide substitution at codon 31 was detected. This nucleotide substitution was seen in 30% of normal controls and was considered as a kind of polymorphism. Less