Achuthan R, Bell S M, Carr I M, Leek J P, Roberts P, Horgan K, Markham A F, Selby P J, MacLennan K A
Molecular Medicine Unit, University of Leeds, St. James's University Hospital, Leeds LS9 7TF, UK.
J Pathol. 2002 Jan;196(1):59-66. doi: 10.1002/path.1015.
BCL10 is a tumour suppressor gene originally cloned from a t(1;14)(p22;q32) breakpoint in a case of mucosa-associated lymphoid tissue (MALT) lymphoma. Translocations involving this gene, though uncommon, are sometimes encountered in MALT lymphomas. This gene is thought to play an important role in the development of malignant lymphomas. Fluorescence in situ hybridization (FISH) was therefore undertaken on 22 cases of malignant lymphoma of varying histology to establish the incidence of rearrangements involving the BCL10 gene. Initially, one case with a novel t(1;2)(p22;p12) translocation involving the BCL10 gene was identified, in a marginal zone lymphoma of the MALT type, and was reported elsewhere. Seven other cases were subsequently identified with abnormalities in the 1p region, including a translocation with a breakpoint in the 1p22 region in a case of lymphoblastic lymphoma. However, none of these involved the BCL10 gene. Mutation analysis of BCL10 was then performed on 57 cases of malignant lymphoma, including 17 MALT lymphomas, by single-strand conformational polymorphism (SSCP) analysis of tumour DNA. Tissue was obtained for mutation analysis for 12 of the 22 cases analysed by FISH. Selected cases with SSCP band shifts were further studied by direct sequencing. Polymorphisms were identified in eight cases, but no mutations of pathogenic significance were identified. Further RT-PCR and mutation analysis was performed on cDNAs from 12 cases (four MALT, seven diffuse large B-cell lymphoma, one Hodgkin's disease) in which DNA analysis had already been completed. This included the MALT lymphoma with the t(1;2)(p22;p12) rearrangement. Again, no mutations were identified in the coding sequence. This study confirms that rearrangements of the BCL10 gene are uncommon in lymphoma (1/22) and may be limited tothe MALT subtype of non-Hodgkin's lymphomas. It was also found that breakpoints or rearrangements in the 1p22 region do not necessarily involve the BCL10 gene. Moreover, the absence of mutations at both the DNA (0/60) and the mRNA (0/12) level indicates that this gene is not frequently inactivated by mutation, in those tumours in which it is not involved in translocations. Our findings suggest that the BCL10 gene is unlikely to have a frequent or key role in general lymphomagenesis.
BCL10是一种肿瘤抑制基因，最初是从一例黏膜相关淋巴组织（MALT）淋巴瘤的t(1;14)(p22;q32)断点处克隆得到的。涉及该基因的易位虽然不常见，但在MALT淋巴瘤中有时会遇到。该基因被认为在恶性淋巴瘤的发生发展中起重要作用。因此，对22例不同组织学类型的恶性淋巴瘤进行了荧光原位杂交（FISH），以确定涉及BCL10基因重排的发生率。最初，在一例MALT型边缘区淋巴瘤中发现了一例涉及BCL10基因的新型t(1;2)(p22;p12)易位，并已在其他地方报道。随后又发现了其他7例1p区域异常的病例，包括一例淋巴细胞淋巴瘤中1p22区域有断点的易位。然而，这些均未涉及BCL10基因。然后，通过对肿瘤DNA进行单链构象多态性（SSCP）分析，对57例恶性淋巴瘤（包括17例MALT淋巴瘤）进行了BCL10的突变分析。在通过FISH分析的22例病例中，有12例获得了用于突变分析的组织。对具有SSCP条带移位的选定病例进一步进行直接测序。在8例中鉴定出多态性，但未鉴定出具有致病意义的突变。对12例（4例MALT、7例弥漫性大B细胞淋巴瘤、1例霍奇金病）已完成DNA分析的病例的cDNA进行了进一步的RT-PCR和突变分析。这包括具有t(1;2)(p22;p12)重排的MALT淋巴瘤。同样，在编码序列中未鉴定出突变。本研究证实，BCL10基因重排在淋巴瘤中不常见（1/22），可能仅限于非霍奇金淋巴瘤的MALT亚型。还发现1p22区域的断点或重排不一定涉及BCL10基因。此外，在DNA水平（0/60）和mRNA水平（0/12）均未发现突变，这表明在那些未参与易位的肿瘤中，该基因不常因突变而失活。我们的研究结果表明，BCL10基因在一般淋巴瘤发生中不太可能起频繁或关键作用。
