Establishment of a novel human B-cell line (OZ) with t(14;18)(q32;q21) and aberrant p53 expression was associated with the homozygous deletions of p15INK4B and p16INK4A genes.
The novel human pre-B cell line OZ was established from a patient with an aggressive form of non-Hodgkin's lymphoma. Karyotypic analysis of both the primary tumour and OZ cells revealed several marker chromosomes, including the t(14;18)(q32;q21) translocation, which involves the Bcl-2 gene, and alterations on chromosome 17p. Southern blot analysis found identical rearrangements in the 5' region of Bcl-2 gene in the primary tumour and OZ cells. Homozygous deletions of the p15INK4B and p16INK4A genes, however, were present only in OZ cells. Western blot analysis detected aberrant small molecular-weight p53 proteins in both cell types. In addition, OZ cells no longer expressed the CD20 antigen. These findings suggest that Bcl-2 gene rearrangement and aberrant p53 expression resulted in the original B-cell tumour. A subsequent transforming event involving the p15INK4B and p16INK4A genes may have generated more immature cells with a growth advantage during in vitro culture. The genetic alterations involving p53, p15INK4B, and p16INK4A may be implicated in the aggressive form of t(14;18)(q32;q21)-bearing tumours and their poor prognosis.
Nagai
M
M
First Department of Internal Medicine, Kagawa Medical University, Japan.
Fujita
M
M
Ohmori
M
M
Matsubara
S
S
Taniwaki
M
M
Horiike
S
S
Tasaka
T
T
Koeffler
H P
HP
Takahara
J
J
D000328:Adult; D000782:Aneuploidy; D018951:Antigens, CD20 / Q000096:biosynthesis / Q000235:genetics; D001402:B-Lymphocytes / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000032:analysis; D001853:Bone Marrow / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins; D002869:Chromosome Aberrations; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics / Q000648:ultrastructure*; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics / Q000648:ultrastructure*; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000172:deficiency; D004273:DNA, Neoplasm / Q000235:genetics; D017809:Fatal Outcome; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D019254:Genes, bcl-2; D019942:Genes, p16; D016158:Genes, p53; D006720:Homozygote; D006801:Humans; D007621:Karyotyping; D008198:Lymph Nodes / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000473:pathology*; D008297:Male; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000032:analysis / Q000172:deficiency / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics*; D014407:Tumor Cells, Cultured / Q000166:cytology; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D025521:Tumor Suppressor Proteins
D018951:Antigens, CD20; D014408:Biomarkers, Tumor; C493966:CDKN2B protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins