p53 gene mutations in multiple myeloma.

Centre for Haematological Oncology, General Infirmary at Leeds.
Molecular Pathology 03/1997; 50(1):18-20. DOI: 10.1136/mp.50.1.18
Source: PubMed

ABSTRACT To assess whether p53 gene mutation is important in the pathogenesis and progression of multiple myeloma.
Thirty eight DNA samples (derived predominantly from bone marrow) obtained from 31 patients with multiple myeloma were examined for mutations in p53 exons 5-9 by polymerase chain reaction single strand conformation polymorphism. Twenty three samples were analysed at the time of diagnosis (one patient had plasma cell leukaemia), three in plateau phase, and 12 at relapse (one plasma cell leukaemia and one extramedullary relapse).
One p53 mutation was detected in this group of patients (3.2%). This was seen in the diagnostic bone marrow sample of a 35 year old man with stage IIA disease and occurred in exon 6 as a result of a silent A to G transition at codon 213 (CGA-->CGG), a polymorphism that has been reported in about 3% of breast and lung tumours.
p53 gene mutations are rare events in multiple myeloma and would seem to be of limited value as a prognostic factor.

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Available from: James ANTHONY Child, Feb 04, 2015
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    • "The correlation of mutations of p53 with detectable protein in lymphoid tumours is poor and therefore it seems preferable to restrict interpretation of data to studies were mutations have been measured. Studies of p53 in myeloma show a mutation rate of 2–4% (Preudhomme et al, 1992; Owen et al, 1997), although the frequency in end stage disease and in myeloma cell lines increases to 40%. This is reflected in studies of serial samples where p53 mutations identified in the terminal stage of disease were not found in samples from the plateau phase (Neri et al, 1993), suggesting a multi-step process with p53 mutation as a late event in tumour progression. "
    British Journal of Haematology 01/1998; 99(4):719-25. DOI:10.1046/j.1365-2141.1997.3793193.x · 4.71 Impact Factor
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    Molecular Pathology 12/1997; 50(6):329. DOI:10.1136/mp.50.6.329-a
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    ABSTRACT: Multiple myeloma (MM) is a B-cell neoplasm characterized by bone marrow infiltration with malignant plasma cells, which synthesize and secrete monoclonal immunoglobulin (Ig) fragments. Despite the considerable progress in the understanding of MM biology, the molecular basis of the disease remains elusive. The initial transformation is thought to occur in a postgerminal center B-lineage cell, carrying a somatically hypermutated Ig heavy chain (IGH) gene. This plasmablastic precursor cell colonizes the bone marrow, propagates clonally and differentiates into a slowly proliferating myeloma cell population, all under the influence of specific cell adhesion molecules and cytokines. Production of interleukin-6 by stromal cells, osteoblasts and, in some cases, neoplastic cells is an essential element of myeloma cell growth, with the cytokine stimulus being delivered intracellularly via the Jack-STAT and ras signaling pathways. While karyotypic changes have been identified in up to 50% of MM patients, recent molecular cytogenetic techniques have revealed chromosomal abnormalities in the vast majority of examined cases. Translocations mostly involve illegal switch rearrangements of the IGH locus with various partner genes (CCND1, FGFR3, c-maf). Such events have been assigned a critical role in MM development. Mutations in coding and regulatory regions, as well as aberrant expression patterns of several oncogenes (c-myc, ras) and tumor suppressor genes (p16, p15) have been reported. Key regulators of programmed cell death (BCL-2, Fas), tumor expansion (metalloproteinases) and drug responsiveness (topoisomerase II alpha) have also been implicated in the pathogenesis of this hematologic malignancy. A tumorigenic role for human herpesvirus 8 (HHV8) was postulated recently, following the detection of viral sequences in bone marrow dendritic cells of MM patients. However, since several research groups were unable to confirm this observation, the role of HHV8 remains unclear. Translation of the advances in MM molecular biology into novel therapeutic strategies is essential in order to improve disease prognosis.
    Annals of Oncology 11/2000; 11(10):1217-28. DOI:10.1023/A:1008331714186 · 7.04 Impact Factor
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