To determine whether the BCL10 mutation plays a role in the oncogenesis of plasma cell dyscrasias, we used polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and direct sequencing analysis and examined the genomic BCL10 mutations in 57 patients with multiple myeloma or plasma cell leukemia and 52 normal bone marrow samples. We found three polymorphic sequence variants, either alone or in combination, at codons 5 and 8, and in intron 1 at base 58 of the BCL10 gene in 37 patients with plasma cell dyscrasia. Identical aberrant band shifts were also observed in 34 normal marrow samples. No polymorphic variants were identified in exon 2 or 3 in either patient or control samples, and no pathogenic mutations were detected. Patients with plasma cell dyscrasias in Taiwan appeared to have a higher frequency of polymorphisms at codon 5 and intron 1 at base 58, and a lower frequency at codons 8 and 213. Our results suggest that BCL10 is not involved in the oncogenesis of plasma cell dyscrasias.
[Show abstract][Hide abstract] ABSTRACT: Malignant transformation of B cells can occur at various steps of lymphocyte development, starting from early B-cell progenitors up to mature B cells, which reflects the heterogeneity of B-cell malignancies with regard to their biologic and clinical behavior. The genetic characterization of B-cell neoplasms during the past two decades has elucidated the mechanisms underlying B-cell lymphomagenesis and led to a more precise definition of lymphoma subgroups. This progress is reflected in the upcoming World Health Organization classification for hematologic neoplasms, which stresses the diagnostic importance of recurrent genetic alterations in leukemias and lymphomas. In the recent past, several genes deregulated by such recurrent chromosomal aberrations have been identified. In addition, the recent introduction of microarray technology has now allowed a more global assessment of gene dysregulation in B-cell oncogenesis and provided a new means for more exactly defining the molecular hallmarks of distinct lymphoma subtypes. This review will focus on recently described molecular features of B-cell lymphomas discovered by the application of new molecular cytogenetic techniques, advanced breakpoint cloning strategies, and microarray approaches.
Current Opinion in Oncology 10/2001; 13(5):316-24. DOI:10.1097/00001622-200109000-00002 · 4.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BCL10, a gene involved in apoptosis signaling, has recently been identified at chromosome 1p22. This gene was found to be mutated in several types of lymphomas and other kinds of solid tumors. Especially in hepatocellular carcinoma, high mutation rates have been reported. These findings suggest that its inactivation may play an important pathogenetic role in tumorigenesis. Furthermore, abnormalities of chromosome 1 where the BCL10 gene is located are a common feature in pediatric solid tumors. Therefore, we analyzed 95 pediatric solid cancers for genomic BCL10 mutations.
Three exons, which encode the whole coding region, were examined in 95 tumor tissues by PCR-SSCP method. Samples revealing aberrant band patterns were subjected to direct sequencing analysis.
A total of six nucleotide changes were detected. Two were in intron 1 (IVS1 + 11C > G, IVS1 + 58G > C) and four were in exons 1 or 3 (Ala5Ser, Leu8Leu, Thr162Met and Gly213Glu). Of four exonic changes, three at codons 5, 162, and 213 resulted in amino acid substitution. In non-tumor tissues, however, similar mutation types were found, suggesting that all nucleotide changes detected were genetic polymorphisms.
This study represents the first genetic analysis of the BCL10 gene in pediatric solid malignant tumors. Our results suggest that BCL10 mutation as a mechanism involved in tumorigenesis is unlikely to be associated with most childhood malignancies.
Medical and Pediatric Oncology 12/2002; 39(6):543-6. DOI:10.1002/mpo.10156
[Show abstract][Hide abstract] ABSTRACT: Multiple myeloma, a neoplasm of plasma cells, accounts for approximately approximately 15% of lymphatohematopoietic cancers (LHC) and 2% of all cancers in the US. Incidence rates increase with age, particularly after age 40, and are higher in men, particularly African American men. The etiology is unknown with no established lifestyle, occupational or environmental risk factors. Although several factors have been implicated as potentially etiologic, findings are inconsistent. We reviewed epidemiologic studies that evaluated lifestyle, dietary, occupational and environmental factors; immune function, family history and genetic factors; and the hypothesized precursor, monoclonal gammopathies of undetermined significance (MGUS). Because multiple myeloma is an uncommon disease, etiologic assessments can be difficult because of small numbers of cases in occupational cohort studies, and few subjects reporting exposure to specific agents in case-control studies. Elevated risks have been reported consistently among persons with a positive family history of LHC. A few studies have reported a relationship between obesity and multiple myeloma, and this may be a promising area of research. Factors underlying higher incidence rates of multiple myeloma in African Americans are not understood. The progression from MGUS to multiple myeloma has been reported in several studies; however, there are no established risk factors for MGUS. To improve our understanding of the causes of multiple myeloma, future research efforts should seek the causes of MGUS. More research is also needed on the genetic factors of multiple myeloma, given the strong familial clustering of the disease.
International Journal of Cancer 01/2007; 120 Suppl 12(S12):40-61. DOI:10.1002/ijc.22718 · 5.09 Impact Factor
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